Is ANKRD1 p.Pro255fs (c.764del) pathogenic?

ANKRD1 p.Pro255fs (c.764del) is classified Uncertain significance in ANKRD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-05). Very rare (popmax 0.00119%, nfe); Associated with ANKRD1-related dilated cardiomyopathy.

What condition is associated with ANKRD1 p.Pro255fs (c.764del)?

ANKRD1 p.Pro255fs (c.764del) is associated with ANKRD1-related dilated cardiomyopathy (ClinVar).

How common is ANKRD1 p.Pro255fs (c.764del) in the general population?

ANKRD1 p.Pro255fs (c.764del) is very rare (popmax 0.00119%, nfe) (gnomAD).

ANKRD1 p.Pro255fs

c.764del · rs753476942 · VCV664045

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Conditions

ANKRD1-related dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.2	GERP -5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,968 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000958% 14/1,461,746 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.Pro255fs
Coding: c.764del
MANE Select: NM_014391
dbSNP: rs753476942
Type: Deletion
Location: chr10:90915628 (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.Pro255Leu Uncertain significance ★ ⚠ same residue
ANKRD1 p.Pro255= Likely benign ★ same residue
ANKRD1 p.Pro52fs Uncertain significance ★★ same condition
ANKRD1 c.345+17del Benign ★★ same condition
ANKRD1 c.346-14_346-9del Benign/Likely benign ★★ same condition
ANKRD1 c.346-17_346-12del Likely benign ★★ same condition
ANKRD1 c.346-18_346-9del Likely benign ★★ same condition
ANKRD1 c.346-21_346-12del Likely benign ★★ 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-pro255fs (accessed [today's date]).

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