Is ANKRD1 p.Asp253Glu (c.759T>A) pathogenic?

ANKRD1 p.Asp253Glu (c.759T>A) is classified Uncertain significance in ANKRD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.9756); Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ANKRD1 p.Asp253Glu (c.759T>A)?

ANKRD1 p.Asp253Glu (c.759T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ANKRD1 p.Asp253Glu (c.759T>A) in the general population?

ANKRD1 p.Asp253Glu (c.759T>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ANKRD1 p.Asp253Glu (c.759T>A)?

AlphaMissense predicts likely pathogenic (score 0.9756) — an in-silico prediction, not a clinical call.

ANKRD1 p.Asp253Glu

c.759T>A · rs139885263 · VCV1380608

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9756	likely pathogenic · top 7% in ANKRD1
REVEL	0.378	indeterminate
SaProt	LLR -9.41	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 -2.1	GERP -5
Regional constraint	o/e 0.93	unconstrained · MANE · 8,158 bp · p 0.17 · regional, not allelic
Overall
CADD	17.27	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 0.00267% African / African-American · 2/74,894 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,796 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.Asp253Glu
Coding: c.759T>A
MANE Select: NM_014391
dbSNP: rs139885263
Type: single nucleotide variant
Location: chr10:90915633 (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

Similar variants

ANKRD1 p.Asp253= Likely benign ★ same residue
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.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-asp253glu (accessed [today's date]).

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