Is ANKRD1 p.Pro288= (c.864G>A) pathogenic?

ANKRD1 p.Pro288= (c.864G>A) is classified Likely benign in ANKRD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-19). Very rare (popmax 0.00801%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ANKRD1 p.Pro288= (c.864G>A)?

ANKRD1 p.Pro288= (c.864G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ANKRD1 p.Pro288= (c.864G>A) in the general population?

ANKRD1 p.Pro288= (c.864G>A) is very rare (popmax 0.00801%, afr) (gnomAD).

ANKRD1 p.Pro288=

c.864G>A · rs758584429 · VCV2904346

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.1	GERP -5
Overall
CADD	4.054	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,902 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00409% 66/1,613,866 alleles · very rare exomes 61/1,461,704 · genomes 5/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,484
European (non-Finnish)	0.00483%	20,700
East Asian	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,478
Finnishnot grpmax-eligible	0.00156%	64,024

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.Pro288=
Coding: c.864G>A
MANE Select: NM_014391
dbSNP: rs758584429
Type: single nucleotide variant
Location: chr10:90912962 (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.Pro288Leu Uncertain significance ★★ ⚠ 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-pro288 (accessed [today's date]).

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