Is SGCD p.Pro244Leu (c.731C>T) pathogenic?

SGCD p.Pro244Leu (c.731C>T) is classified Uncertain significance in SGCD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-02-08). AlphaMissense: likely benign (0.1633); Very rare (popmax 0.00729%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2F.

How common is SGCD p.Pro244Leu (c.731C>T) in the general population?

SGCD p.Pro244Leu (c.731C>T) is very rare (popmax 0.00729%, nfe) (gnomAD).

What do computational predictors say about SGCD p.Pro244Leu (c.731C>T)?

AlphaMissense predicts likely benign (score 0.1633) — an in-silico prediction, not a clinical call.

SGCD p.Pro244Leu

Q: What condition is associated with SGCD p.Pro244Leu (c.731C>T)?

SGCD p.Pro244Leu (c.731C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2F, dilated cardiomyopathy 1L (ClinVar).

Q: How is Delta-sarcoglycan-related limb-girdle muscular dystrophy R6 inherited?

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

c.731C>T · rs375159661 · VCV43356

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1633 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2F

Computational evidence

Protein change
AlphaMissense	0.1633	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -9.47	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	21.8	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 P243L vs ClinVar P244L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00729% European (non-Finnish) · 86/1,179,758 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00539% 87/1,613,652 alleles · very rare exomes 83/1,461,528 · genomes 4/152,124 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,718
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Pro244Leu
Coding: c.731C>T
MANE Select: NM_000337
dbSNP: rs375159661
Type: single nucleotide variant
Location: chr5:156759248 (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

autosomal recessive limb-girdle muscular dystrophy type 2F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1L

For Delta-sarcoglycan-related limb-girdle muscular dystrophy R6 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

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
SGCD c.4-1G>T Likely pathogenic ★★ same condition
SGCD p.Arg33Ter Pathogenic/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-pro244leu (accessed [today's date]).

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