Is AIDA p.Glu265Val (c.794A>T) pathogenic?

AIDA p.Glu265Val (c.794A>T) is classified Uncertain significance in AIDA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely pathogenic (0.9958); Very rare (popmax 0.00446%, eas).

How common is AIDA p.Glu265Val (c.794A>T) in the general population?

AIDA p.Glu265Val (c.794A>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about AIDA p.Glu265Val (c.794A>T)?

AlphaMissense predicts likely pathogenic (score 0.9958) — an in-silico prediction, not a clinical call.

AIDA p.Glu265Val

c.794A>T · rs1422839954 · VCV2548835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9958	likely pathogenic · top 10% in AIDA
REVEL	0.608	indeterminate
SaProt	LLR -12.56	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 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 345 bp · p 2.7e-06 · regional, not allelic
Overall
CADD	26.6	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

Grpmax group 0.00446% East Asian · 2/44,870 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,613,980 alleles · very rare

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: AIDA
Protein: p.Glu265Val
Coding: c.794A>T
MANE Select: NM_022831
dbSNP: rs1422839954
Type: single nucleotide variant
Location: chr1:222670163 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.37
Residue 265: the c2 aida-type domain

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

Similar variants

AIDA p.Asn51Ser Uncertain significance ★ ⚠ same type
AIDA p.Asp134Tyr Uncertain significance ★ ⚠ same type
AIDA p.Asp186Asn Uncertain significance ★ ⚠ same type
AIDA p.Cys69Arg Uncertain significance ★ ⚠ same type
AIDA p.Glu45Lys Uncertain significance ★ ⚠ same type
AIDA p.Gly198Ser Uncertain significance ★ ⚠ same type
AIDA p.Gly236Asp Uncertain significance ★ ⚠ same type
AIDA p.Ile120Asn 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/aida-p-glu265val (accessed [today's date]).

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