Is C8G p.Asp131Val (c.392A>T) pathogenic?

C8G p.Asp131Val (c.392A>T) is classified Uncertain significance in C8G (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely pathogenic (0.7554); Absent from gnomAD v4.1.

How common is C8G p.Asp131Val (c.392A>T) in the general population?

C8G p.Asp131Val (c.392A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C8G p.Asp131Val (c.392A>T)?

AlphaMissense predicts likely pathogenic (score 0.7554) — an in-silico prediction, not a clinical call.

C8G p.Asp131Val

c.392A>T · rs2491362822 · VCV2252291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7554 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7554	likely pathogenic · top 9% in C8G
REVEL	0.429	indeterminate
SaProt	LLR -13.94	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.3, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 1,457 bp · p 0.046 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C8G
Protein: p.Asp131Val
Coding: c.392A>T
MANE Select: NM_000606
dbSNP: rs2491362822
Type: single nucleotide variant
Location: chr9:136946130 (GRCh38)
Gene constraint: LOEUF 1.809 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.06 · 15 PDB
Residue 131: a disulfide bond

Full C8G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C8G p.Tyr181His Uncertain significance ★★ ⚠ same type
C8G c.276-3C>T Likely benign ★★ same type
C8G p.Arg69Gln Benign ★★ same type
C8G p.Val196Ile Likely benign ★★ same type
C8G p.Ala128Thr Uncertain significance ★ ⚠ same type
C8G p.Ala136Thr Uncertain significance ★ ⚠ same type
C8G p.Ala143Val Uncertain significance ★ ⚠ same type
C8G p.Ala16Val Uncertain significance ★ ⚠ same type

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/c8g-p-asp131val (accessed [today's date]).

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