Is ANKRD1 p.Cys234Ser (c.700T>A) pathogenic?

ANKRD1 p.Cys234Ser (c.700T>A) is classified Uncertain significance in ANKRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely pathogenic (0.64); Very rare (popmax 0.00017%, nfe); Associated with ANKRD1-related dilated cardiomyopathy.

What condition is associated with ANKRD1 p.Cys234Ser (c.700T>A)?

ANKRD1 p.Cys234Ser (c.700T>A) is associated with ANKRD1-related dilated cardiomyopathy (ClinVar).

How common is ANKRD1 p.Cys234Ser (c.700T>A) in the general population?

ANKRD1 p.Cys234Ser (c.700T>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ANKRD1 p.Cys234Ser (c.700T>A)?

AlphaMissense predicts likely pathogenic (score 0.64) — an in-silico prediction, not a clinical call.

ANKRD1 p.Cys234Ser

c.700T>A · rs1208163863 · VCV2705293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.64 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ANKRD1-related dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.64	likely pathogenic
REVEL	0.605	indeterminate
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,158 bp · p 0.17 · regional, not allelic
Overall
CADD	28.7	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,926 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,758 alleles · very rare

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: ANKRD1
Protein: p.Cys234Ser
Coding: c.700T>A
MANE Select: NM_014391
dbSNP: rs1208163863
Type: single nucleotide variant
Location: chr10:90915832 (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.Cys234= Likely benign ★★ same residue
ANKRD1 p.Cys234Arg 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

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-cys234ser (accessed [today's date]).

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