Is SGCD p.Phe139Ile (c.415T>A) pathogenic?

SGCD p.Phe139Ile (c.415T>A) is classified Uncertain significance in SGCD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-01-11). AlphaMissense: ambiguous (0.5494); Very rare (popmax 8.49e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SGCD p.Phe139Ile (c.415T>A)?

SGCD p.Phe139Ile (c.415T>A) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2F, dilated cardiomyopathy 1L (ClinVar).

How common is SGCD p.Phe139Ile (c.415T>A) in the general population?

SGCD p.Phe139Ile (c.415T>A) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about SGCD p.Phe139Ile (c.415T>A)?

AlphaMissense predicts ambiguous (score 0.5494) — an in-silico prediction, not a clinical call.

SGCD p.Phe139Ile

c.415T>A · rs886044160 · VCV289355

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5494 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5494	ambiguous
REVEL	0.659	pathogenic-leaning
SaProt	LLR -11.63	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F138I vs ClinVar F139I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,500 alleles

Overall 6.2e-05% 1/1,611,702 alleles · very rare exomes 1/1,459,574 · genomes 0/152,128 · joint denominator

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.Phe139Ile
Coding: c.415T>A
MANE Select: NM_000337
dbSNP: rs886044160
Type: single nucleotide variant
Location: chr5:156594964 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2F dilated cardiomyopathy 1L

Similar variants

SGCD p.Phe139fs Pathogenic ★ 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
SGCD c.4-1G>T 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-phe139ile (accessed [today's date]).

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