Is AHSG p.Asp296Ala (c.887A>C) pathogenic?

AHSG p.Asp296Ala (c.887A>C) is classified Uncertain significance in AHSG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.0663); Very rare (popmax 6.84e-05%).

How common is AHSG p.Asp296Ala (c.887A>C) in the general population?

AHSG p.Asp296Ala (c.887A>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about AHSG p.Asp296Ala (c.887A>C)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

AHSG p.Asp296Ala

c.887A>C · VCV4639425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -4.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -2.6, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 7,785 bp · p 0.66 · regional, not allelic
Overall
CADD	1.135	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 6.84e-05%

Overall 6.84e-05% 1/1,461,894 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: AHSG
Protein: p.Asp296Ala
Coding: c.887A>C
MANE Select: NM_001622
Type: single nucleotide variant
Location: chr3:186620713 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.59
Residue 296: a disulfide bond; the 'disordered' region

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

Similar variants

AHSG p.Asp296Tyr Likely benign ★ ⚠ same residue
AHSG p.Val342Met Uncertain significance ★★ ⚠ same type
AHSG p.Ala170= Benign/Likely benign ★★ same type
AHSG p.Arg317Cys Benign ★★ ⚠ same type
AHSG p.Met248Thr Benign ★★ same type
AHSG p.Ser256Thr Benign ★★ same type
AHSG p.Thr270= Benign ★★ same type
AHSG p.Val142Leu Benign ★★ ⚠ 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/ahsg-p-asp296ala (accessed [today's date]).

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