Is SGCD p.Ala239Val (c.716C>T) pathogenic?

SGCD p.Ala239Val (c.716C>T) is classified Uncertain significance in SGCD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-02-08). AlphaMissense: likely benign (0.122); Ultra-rare (popmax 0.0111%, eas); Associated with dilated cardiomyopathy 1L.

How common is SGCD p.Ala239Val (c.716C>T) in the general population?

SGCD p.Ala239Val (c.716C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SGCD p.Ala239Val (c.716C>T)?

AlphaMissense predicts likely benign (score 0.122) — an in-silico prediction, not a clinical call.

SGCD p.Ala239Val

Q: What condition is associated with SGCD p.Ala239Val (c.716C>T)?

SGCD p.Ala239Val (c.716C>T) is associated with dilated cardiomyopathy 1L, autosomal recessive limb-girdle muscular dystrophy type 2F, qualitative or quantitative defects of delta-sarcoglycan (ClinVar).

c.716C>T · rs377153196 · VCV352336

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.122 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

dilated cardiomyopathy 1L

Computational evidence

Protein change
AlphaMissense	0.122	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.22	acceptor loss, 16 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6	GERP 0.74, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A238V vs ClinVar A239V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,882 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00304% 49/1,613,452 alleles · ultra-rare exomes 41/1,461,284 · genomes 8/152,168 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,741
East Asiangrpmax	0.0111%	8,976
Remaining individualsnot grpmax-eligible	0.0032%	31,226
European (non-Finnish)	0.00212%	47,183

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SGCD
Protein: p.Ala239Val
Coding: c.716C>T
MANE Select: NM_000337
dbSNP: rs377153196
Type: single nucleotide variant
Location: chr5:156759233 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 81.43

Full SGCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1L — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2F qualitative or quantitative defects of delta-sarcoglycan

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

SGCD p.Ala239= Conflicting classifications of pathogenicity ★ same residue
SGCD p.Ala239Thr Uncertain significance ★ ⚠ same residue
SGCD p.Arg165Ter Pathogenic ★★★ same condition
SGCD p.Arg97Ter Pathogenic ★★★ same condition
SGCD p.Arg31Trp Uncertain significance ★★★ ⚠ same condition
SGCD p.Ile64Thr Uncertain significance ★★★ ⚠ same condition
SGCD c.192+1G>A Likely pathogenic ★★ same condition
SGCD c.294+1G>A Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sgcd-p-ala239val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown