Is AK7 p.Ala331Val (c.992C>T) pathogenic?

AK7 p.Ala331Val (c.992C>T) is classified Uncertain significance in AK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-22). AlphaMissense: likely pathogenic (0.6281); Very rare (popmax 0.00226%, eas).

How common is AK7 p.Ala331Val (c.992C>T) in the general population?

AK7 p.Ala331Val (c.992C>T) is very rare (popmax 0.00226%, eas) (gnomAD).

What do computational predictors say about AK7 p.Ala331Val (c.992C>T)?

AlphaMissense predicts likely pathogenic (score 0.6281) — an in-silico prediction, not a clinical call.

AK7 p.Ala331Val

c.992C>T · rs373425925 · VCV2197335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6281 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00226%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6281	likely pathogenic
REVEL	0.154	moderately benign-leaning
SaProt	LLR -11.35	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP 0.32, phastCons 0.62
Regional constraint	o/e 0.96	unconstrained · MANE · 96 kb · p 0.27 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00226% East Asian · 1/44,232 alleles

Filtering AF 0.000694% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000543%

Overall 0.00113% 18/1,595,798 alleles · very rare exomes 16/1,443,636 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00226%	44,232
Remaining individualsnot grpmax-eligible	0.00162%	61,640
African / African-American	0.00134%	74,382
European (non-Finnish)	0.0012%	83,588
South Asian	0.00114%	87,910

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: AK7
Protein: p.Ala331Val
Coding: c.992C>T
MANE Select: NM_152327
dbSNP: rs373425925
Type: single nucleotide variant
Location: chr14:96451464 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35

Full AK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AK7 p.Ala331= Benign ★ same residue
AK7 p.Ala626Val Uncertain significance ★★ ⚠ same type
AK7 p.Ala675Val Uncertain significance ★★ ⚠ same type
AK7 p.Arg108His Uncertain significance ★★ ⚠ same type
AK7 p.Arg341Gln Uncertain significance ★★ ⚠ same type
AK7 p.Arg552Gln Uncertain significance ★★ ⚠ same type
AK7 p.Arg629Gln Uncertain significance ★★ ⚠ same type
AK7 p.Arg632Gly 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/ak7-p-ala331val (accessed [today's date]).

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