Is ANKRD1 p.Glu130Val (c.389A>T) pathogenic?

ANKRD1 p.Glu130Val (c.389A>T) is classified Uncertain significance in ANKRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-22). AlphaMissense: ambiguous (0.4609); Absent from gnomAD v4.1; Associated with ANKRD1-related dilated cardiomyopathy.

What condition is associated with ANKRD1 p.Glu130Val (c.389A>T)?

ANKRD1 p.Glu130Val (c.389A>T) is associated with ANKRD1-related dilated cardiomyopathy (ClinVar).

How common is ANKRD1 p.Glu130Val (c.389A>T) in the general population?

ANKRD1 p.Glu130Val (c.389A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD1 p.Glu130Val (c.389A>T)?

AlphaMissense predicts ambiguous (score 0.4609) — an in-silico prediction, not a clinical call.

ANKRD1 p.Glu130Val

c.389A>T · rs1321608531 · VCV2198960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4609 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ANKRD1-related dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.4609	ambiguous
REVEL	0.432	indeterminate
SaProt	LLR -9.34	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,158 bp · p 0.17 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

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.Glu130Val
Coding: c.389A>T
MANE Select: NM_014391
dbSNP: rs1321608531
Type: single nucleotide variant
Location: chr10:90918929 (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.Glu130Ter 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
ANKRD1 p.Arg100Ser Uncertain significance ★★ ⚠ same condition
ANKRD1 p.Arg154Trp 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-glu130val (accessed [today's date]).

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