Is ANKRD1 p.Arg315His (c.944G>A) pathogenic?

ANKRD1 p.Arg315His (c.944G>A) is classified Conflicting classifications of pathogenicity in ANKRD1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-11). AlphaMissense: likely benign (0.1124); Ultra-rare (popmax 0.0183%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ANKRD1 p.Arg315His (c.944G>A)?

ANKRD1 p.Arg315His (c.944G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ANKRD1 p.Arg315His (c.944G>A) in the general population?

ANKRD1 p.Arg315His (c.944G>A) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about ANKRD1 p.Arg315His (c.944G>A)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

ANKRD1 p.Arg315His

c.944G>A · rs746392266 · VCV201669

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 8,158 bp · p 0.17 · regional, not allelic
Overall
CADD	22.3	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 0.0183% Admixed American · 11/59,990 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00242% 39/1,613,700 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,454
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
Remaining individualsnot grpmax-eligible	0.0032%	31,235
European (non-Finnish)	0.00203%	49,156
African / African-American	0.00134%	74,904

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.Arg315His
Coding: c.944G>A
MANE Select: NM_014391
dbSNP: rs746392266
Type: single nucleotide variant
Location: chr10:90912882 (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.Arg315Cys Uncertain significance ★★ ⚠ same residue
ANKRD1 p.Arg315Ser Uncertain significance ★ ⚠ same residue
ANKRD1 p.Arg315Leu Uncertain significance ★ ⚠ same residue
ANKRD1 p.Arg315Pro Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg315his (accessed [today's date]).

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