Is ANKRD31 p.Ala42Val (c.125C>T) pathogenic?

ANKRD31 p.Ala42Val (c.125C>T) is classified Uncertain significance in ANKRD31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0833); Absent from gnomAD v4.1.

How common is ANKRD31 p.Ala42Val (c.125C>T) in the general population?

ANKRD31 p.Ala42Val (c.125C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD31 p.Ala42Val (c.125C>T)?

AlphaMissense predicts likely benign (score 0.0833) — an in-silico prediction, not a clinical call.

ANKRD31 p.Ala42Val

c.125C>T · VCV4640870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0833	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -5.74	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 2.5	GERP -1.8, phastCons 0.067
Regional constraint	o/e 0.92	unconstrained · MANE · 168 kb · p 0.00044 · regional, not allelic
Overall
CADD	12.62	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

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: ANKRD31
Protein: p.Ala42Val
Coding: c.125C>T
MANE Select: NM_001372053
Type: single nucleotide variant
Location: chr5:75230615 (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-ala42val (accessed [today's date]).

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