Is ANKRD1 p.Ala50Asp (c.149C>A) pathogenic?

ANKRD1 p.Ala50Asp (c.149C>A) is classified Uncertain significance in ANKRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely benign (0.0855); Absent from gnomAD v4.1; Associated with ANKRD1-related dilated cardiomyopathy.

What condition is associated with ANKRD1 p.Ala50Asp (c.149C>A)?

ANKRD1 p.Ala50Asp (c.149C>A) is associated with ANKRD1-related dilated cardiomyopathy (ClinVar).

How common is ANKRD1 p.Ala50Asp (c.149C>A) in the general population?

ANKRD1 p.Ala50Asp (c.149C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD1 p.Ala50Asp (c.149C>A)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

ANKRD1 p.Ala50Asp

c.149C>A · rs2492962643 · VCV2838968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ANKRD1-related dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -5.62	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 -0.022	GERP -4.8
Regional constraint	o/e 0.93	unconstrained · MANE · 8,158 bp · p 0.17 · regional, not allelic
Overall
CADD	6.085	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: ANKRD1
Protein: p.Ala50Asp
Coding: c.149C>A
MANE Select: NM_014391
dbSNP: rs2492962643
Type: single nucleotide variant
Location: chr10:90920227 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.64

Full ANKRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ANKRD1-related dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANKRD1 p.Ala50= Benign/Likely benign ★★ same residue
ANKRD1 p.Ala50Pro Benign/Likely benign ★★ same residue
ANKRD1 p.Ala50Ser Uncertain significance ★ ⚠ same residue
ANKRD1 c.651+6C>T Uncertain significance ★★ same condition
ANKRD1 c.652-2A>T Uncertain significance ★★ same condition
ANKRD1 c.849+1G>C Uncertain significance ★★ same condition
ANKRD1 p.Ala175Thr Uncertain significance ★★ ⚠ same condition
ANKRD1 p.Ala259Val Uncertain significance ★★ ⚠ same condition

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/ankrd1-p-ala50asp (accessed [today's date]).

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