Is ANKRD2 p.Arg155Gln (c.464G>A) pathogenic?

ANKRD2 p.Arg155Gln (c.464G>A) is classified Uncertain significance in ANKRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely pathogenic (0.8412); Ultra-rare (popmax 0.0826%, mid).

How common is ANKRD2 p.Arg155Gln (c.464G>A) in the general population?

ANKRD2 p.Arg155Gln (c.464G>A) is ultra-rare (popmax 0.0826%, mid) (gnomAD).

What do computational predictors say about ANKRD2 p.Arg155Gln (c.464G>A)?

AlphaMissense predicts likely pathogenic (score 0.8412) — an in-silico prediction, not a clinical call.

ANKRD2 p.Arg155Gln

c.464G>A · rs144335975 · VCV2369852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8412 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0826%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8412	likely pathogenic
REVEL	0.428	indeterminate
SaProt	LLR -9.70	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 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.092 · regional, not allelic
Overall
CADD	34.0	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 R182Q vs ClinVar R155Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0826% Middle Eastern · 5/6,052 alleles

Filtering AF 0.0325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0211%

Overall 0.00491% 79/1,610,486 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0826%	1,210
African / African-American	0.012%	8,330
East Asian	0.00893%	11,196
South Asian	0.00665%	15,030
European (non-Finnish)	0.00458%	21,827
Remaining individualsnot grpmax-eligible	0.0016%	62,384

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.Arg155Gln
Coding: c.464G>A
MANE Select: NM_001346793
dbSNP: rs144335975
Type: single nucleotide variant
Location: chr10:97580862 (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.Arg155Trp 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-arg155gln (accessed [today's date]).

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