Is ANKRD40 p.Glu299Lys (c.895G>A) pathogenic?

ANKRD40 p.Glu299Lys (c.895G>A) is classified Uncertain significance in ANKRD40 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely pathogenic (0.9752); Absent from gnomAD v4.1.

How common is ANKRD40 p.Glu299Lys (c.895G>A) in the general population?

ANKRD40 p.Glu299Lys (c.895G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD40 p.Glu299Lys (c.895G>A)?

AlphaMissense predicts likely pathogenic (score 0.9752) — an in-silico prediction, not a clinical call.

ANKRD40 p.Glu299Lys

c.895G>A · rs2545993775 · VCV2319445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9752	likely pathogenic · top 10% in ANKRD40
REVEL	0.374	indeterminate
SaProt	LLR -10.27	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 3,422 bp · p 0.0013 · regional, not allelic
Overall
CADD	29.4	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.

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: ANKRD40
Protein: p.Glu299Lys
Coding: c.895G>A
MANE Select: NM_052855
dbSNP: rs2545993775
Type: single nucleotide variant
Location: chr17:50697005 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.38

Full ANKRD40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD40 p.Ala242Thr Uncertain significance ★ ⚠ same type
ANKRD40 p.Ala350Thr Uncertain significance ★ ⚠ same type
ANKRD40 p.Arg13Lys Uncertain significance ★ ⚠ same type
ANKRD40 p.Arg177Gln Uncertain significance ★ ⚠ same type
ANKRD40 p.Arg217Cys Uncertain significance ★ ⚠ same type
ANKRD40 p.Arg347Thr Uncertain significance ★ ⚠ same type
ANKRD40 p.Asn122Lys Uncertain significance ★ ⚠ same type
ANKRD40 p.Asn145Ser 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/ankrd40-p-glu299lys (accessed [today's date]).

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