Is SGCA p.Val332Phe (c.994G>T) pathogenic?

SGCA p.Val332Phe (c.994G>T) is classified Uncertain significance in SGCA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0851); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SGCA p.Val332Phe (c.994G>T)?

SGCA p.Val332Phe (c.994G>T) is associated with Inborn genetic diseases (ClinVar).

How common is SGCA p.Val332Phe (c.994G>T) in the general population?

SGCA p.Val332Phe (c.994G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about SGCA p.Val332Phe (c.994G>T)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

SGCA p.Val332Phe

c.994G>T · rs1031283100 · VCV2241058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.486	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.89	GERP 0.44, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 9,393 bp · p 0.033 · regional, not allelic
Overall
CADD	16.59	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,430 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,604,720 alleles · very rare exomes 2/1,452,352 · genomes 0/152,368 · 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: SGCA
Protein: p.Val332Phe
Coding: c.994G>T
MANE Select: NM_000023
dbSNP: rs1031283100
Type: single nucleotide variant
Location: chr17:50175267 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.15

Full SGCA 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

Similar variants

SGCA p.Val332= Likely benign ★ same residue
SGCA p.Ala220Thr Uncertain significance ★★ ⚠ same condition
SGCA p.Ala290Val Uncertain significance ★★ ⚠ same condition
SGCA p.Arg141His Uncertain significance ★★ ⚠ same condition
SGCA p.Arg156Cys Uncertain significance ★★ ⚠ same condition
SGCA p.Arg156Ser Uncertain significance ★★ ⚠ same condition
SGCA p.Arg184Cys Uncertain significance ★★ ⚠ same condition
SGCA p.Arg192Gln Uncertain significance ★★ ⚠ 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/sgca-p-val332phe (accessed [today's date]).

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