Is ANKRD2 p.Arg155Trp (c.463C>T) pathogenic?

ANKRD2 p.Arg155Trp (c.463C>T) is classified Uncertain significance in ANKRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely pathogenic (0.8792); Very rare (popmax 0.0084%, amr).

How common is ANKRD2 p.Arg155Trp (c.463C>T) in the general population?

ANKRD2 p.Arg155Trp (c.463C>T) is very rare (popmax 0.0084%, amr) (gnomAD).

What do computational predictors say about ANKRD2 p.Arg155Trp (c.463C>T)?

AlphaMissense predicts likely pathogenic (score 0.8792) — an in-silico prediction, not a clinical call.

ANKRD2 p.Arg155Trp

c.463C>T · VCV4055417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0084%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8792	likely pathogenic
REVEL	0.395	indeterminate
SaProt	LLR -11.89	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.48	GERP -3.4, phastCons 0.032
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.092 · regional, not allelic
Overall
CADD	23.7	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R182W vs ClinVar R155W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0084% Admixed American · 5/59,546 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00242% 39/1,610,096 alleles · very rare exomes 35/1,457,954 · genomes 4/152,142 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0084%	11,909
African / African-American	0.00802%	12,473
East Asian	0.00446%	22,401
South Asian	0.00444%	22,539
European (non-Finnish)	0.00187%	53,569

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: ANKRD2
Protein: p.Arg155Trp
Coding: c.463C>T
MANE Select: NM_001346793
Type: single nucleotide variant
Location: chr10:97580861 (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.Arg155Gln Uncertain significance ★ ⚠ same residue
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

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-arg155trp (accessed [today's date]).

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