Is ANKRD1 p.Ala50Ser (c.148G>T) pathogenic?

ANKRD1 p.Ala50Ser (c.148G>T) is classified Uncertain significance in ANKRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely benign (0.0697); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ANKRD1 p.Ala50Ser (c.148G>T)?

ANKRD1 p.Ala50Ser (c.148G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ANKRD1 p.Ala50Ser (c.148G>T) in the general population?

ANKRD1 p.Ala50Ser (c.148G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD1 p.Ala50Ser (c.148G>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

ANKRD1 p.Ala50Ser

c.148G>T · rs28730751 · VCV3226303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.51	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 0.015	GERP -1.4
Regional constraint	o/e 0.93	unconstrained · MANE · 8,158 bp · p 0.17 · regional, not allelic
Overall
CADD	8.209	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKRD1
Protein: p.Ala50Ser
Coding: c.148G>T
MANE Select: NM_014391
dbSNP: rs28730751
Type: single nucleotide variant
Location: chr10:90920228 (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.Ala50= Benign/Likely benign ★★ same residue
ANKRD1 p.Ala50Pro Benign/Likely benign ★★ same residue
ANKRD1 p.Ala50Asp 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

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-ala50ser (accessed [today's date]).

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