Is ANKRD1 p.Leu306Phe (c.916C>T) pathogenic?

ANKRD1 p.Leu306Phe (c.916C>T) is classified Uncertain significance in ANKRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: likely benign (0.248); Very rare (popmax 0.00133%, afr); Associated with ANKRD1-related dilated cardiomyopathy.

What condition is associated with ANKRD1 p.Leu306Phe (c.916C>T)?

ANKRD1 p.Leu306Phe (c.916C>T) is associated with ANKRD1-related dilated cardiomyopathy (ClinVar).

How common is ANKRD1 p.Leu306Phe (c.916C>T) in the general population?

ANKRD1 p.Leu306Phe (c.916C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ANKRD1 p.Leu306Phe (c.916C>T)?

AlphaMissense predicts likely benign (score 0.248) — an in-silico prediction, not a clinical call.

ANKRD1 p.Leu306Phe

c.916C>T · rs1847332132 · VCV850889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.248 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ANKRD1-related dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.248	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,158 bp · p 0.17 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,038 alleles

Overall 6.84e-05% 1/1,461,774 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.Leu306Phe
Coding: c.916C>T
MANE Select: NM_014391
dbSNP: rs1847332132
Type: single nucleotide variant
Location: chr10:90912910 (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 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
ANKRD1 p.Arg154Trp Uncertain significance ★★ ⚠ same condition
ANKRD1 p.Arg66Ter 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-leu306phe (accessed [today's date]).

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