Is ANKRD1 p.Ser187Phe (c.560C>T) pathogenic?

ANKRD1 p.Ser187Phe (c.560C>T) is classified Conflicting classifications of pathogenicity in ANKRD1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-05). AlphaMissense: likely pathogenic (0.9703); Rare (popmax 0.457%, sas); Associated with Cardiovascular phenotype.

What condition is associated with ANKRD1 p.Ser187Phe (c.560C>T)?

ANKRD1 p.Ser187Phe (c.560C>T) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy (ClinVar).

How common is ANKRD1 p.Ser187Phe (c.560C>T) in the general population?

ANKRD1 p.Ser187Phe (c.560C>T) is rare (popmax 0.457%, sas) (gnomAD).

What do computational predictors say about ANKRD1 p.Ser187Phe (c.560C>T)?

AlphaMissense predicts likely pathogenic (score 0.9703) — an in-silico prediction, not a clinical call.

ANKRD1 p.Ser187Phe

c.560C>T · rs397517251 · VCV45635

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.9703 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.457%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9703	likely pathogenic · top 8% in ANKRD1
REVEL	0.383	indeterminate
SaProt	LLR -8.37	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 8.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,158 bp · p 0.17 · regional, not allelic
Overall
CADD	28.9	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 0.457% South Asian · 416/91,058 alleles

Filtering AF 0.421% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.406%

Overall 0.0302% 487/1,613,390 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.457%	219
Remaining individualsnot grpmax-eligible	0.088%	1,136
East Asian	0.0312%	3,204
European (non-Finnish)	0.00017%	589,682

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.Ser187Phe
Coding: c.560C>T
MANE Select: NM_014391
dbSNP: rs397517251
Type: single nucleotide variant
Location: chr10:90916262 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy

Similar variants

ANKRD1 c.207+1G>T Uncertain significance ★★ same condition
ANKRD1 c.27+1G>T Uncertain significance ★★ same condition
ANKRD1 c.28-3T>C Uncertain significance ★★ same condition
ANKRD1 c.651+4T>A Uncertain significance ★★ same condition
ANKRD1 c.651+6C>T Uncertain significance ★★ same condition
ANKRD1 c.750+2T>C Uncertain significance ★★ same condition
ANKRD1 c.750+4A>G Uncertain significance ★★ same condition
ANKRD1 c.751-3T>C 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-ser187phe (accessed [today's date]).

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