Is ANKRD2 p.Trp296Cys (c.888G>C) pathogenic?

ANKRD2 p.Trp296Cys (c.888G>C) is classified Uncertain significance in ANKRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: likely pathogenic (0.9855); Absent from gnomAD v4.1.

How common is ANKRD2 p.Trp296Cys (c.888G>C) in the general population?

ANKRD2 p.Trp296Cys (c.888G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD2 p.Trp296Cys (c.888G>C)?

AlphaMissense predicts likely pathogenic (score 0.9855) — an in-silico prediction, not a clinical call.

ANKRD2 p.Trp296Cys

c.888G>C · rs1421942841 · VCV2295879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9855 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9855	likely pathogenic · top 4% in ANKRD2
REVEL	0.344	indeterminate
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.092 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM W323C vs ClinVar W296C) — verify the residue.

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: ANKRD2
Protein: p.Trp296Cys
Coding: c.888G>C
MANE Select: NM_001346793
dbSNP: rs1421942841
Type: single nucleotide variant
Location: chr10:97583611 (GRCh38)
Gene constraint: LOEUF 1.426 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.30

Full ANKRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD2 p.Ala285= Benign ★★ same type
ANKRD2 p.Pro119Leu Benign/Likely benign ★★ ⚠ same type
ANKRD2 p.Pro6Arg Benign ★★ same type
ANKRD2 p.Ala10Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala128Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala12Thr Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala311Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Arg100Pro 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/ankrd2-p-trp296cys (accessed [today's date]).

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