Is SGCD p.Val265Ile (c.793G>A) pathogenic?

SGCD p.Val265Ile (c.793G>A) is classified Conflicting classifications of pathogenicity in SGCD (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-02-21). AlphaMissense: likely benign (0.0821); Ultra-rare (popmax 0.0254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SGCD p.Val265Ile (c.793G>A)?

SGCD p.Val265Ile (c.793G>A) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2F (ClinVar).

How common is SGCD p.Val265Ile (c.793G>A) in the general population?

SGCD p.Val265Ile (c.793G>A) is ultra-rare (popmax 0.0254%, nfe) (gnomAD).

What do computational predictors say about SGCD p.Val265Ile (c.793G>A)?

AlphaMissense predicts likely benign (score 0.0821) — an in-silico prediction, not a clinical call.

SGCD p.Val265Ile

c.793G>A · rs772185467 · VCV449229

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0821 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0821	likely benign
REVEL	0.685	pathogenic-leaning
SaProt	LLR -9.34	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 1.1, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 430 kb · p 0.031 · regional, not allelic
Overall
CADD	24.5	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 V264I vs ClinVar V265I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0254% European (non-Finnish) · 300/1,179,550 alleles

Filtering AF 0.023% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0221%

Overall 0.0195% 315/1,613,430 alleles · ultra-rare exomes 301/1,461,260 · genomes 14/152,170 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0254%	3,932
Remaining individualsnot grpmax-eligible	0.0112%	8,921
South Asian	0.00549%	18,212
African / African-American	0.00401%	24,964

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.Val265Ile
Coding: c.793G>A
MANE Select: NM_000337
dbSNP: rs772185467
Type: single nucleotide variant
Location: chr5:156759310 (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

Similar variants

SGCD p.Val265Leu 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
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-val265ile (accessed [today's date]).

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