Is ANKRD31 p.Ser892Tyr (c.2675C>A) pathogenic?

ANKRD31 p.Ser892Tyr (c.2675C>A) is classified Uncertain significance in ANKRD31 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.1114); Very rare (popmax 0.00209%, nfe).

How common is ANKRD31 p.Ser892Tyr (c.2675C>A) in the general population?

ANKRD31 p.Ser892Tyr (c.2675C>A) is very rare (popmax 0.00209%, nfe) (gnomAD).

What do computational predictors say about ANKRD31 p.Ser892Tyr (c.2675C>A)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

ANKRD31 p.Ser892Tyr

c.2675C>A · rs531649376 · VCV2244569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00209%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -8.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.62, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 168 kb · p 0.00044 · regional, not allelic
Overall
CADD	17.97	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 0.00209% European (non-Finnish) · 24/1,146,326 alleles

Filtering AF 0.00142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00163% 25/1,536,124 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00209%	47,763
Remaining individualsnot grpmax-eligible	0.00167%	59,950

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: ANKRD31
Protein: p.Ser892Tyr
Coding: c.2675C>A
MANE Select: NM_001372053
dbSNP: rs531649376
Type: single nucleotide variant
Location: chr5:75146736 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.08

Full ANKRD31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD31 p.Arg1353Gln Benign ★★ same type
ANKRD31 p.Asn192Ile Benign ★★ same type
ANKRD31 c.1565-2A>G Pathogenic ★ same type
ANKRD31 p.Gln329Ter Pathogenic ★ same type
ANKRD31 p.Ala1011Asp Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1021Thr Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1294Thr Uncertain significance ★ ⚠ same type
ANKRD31 p.Ala1302Thr 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/ankrd31-p-ser892tyr (accessed [today's date]).

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