Is ANKRD50 p.Val754Ala (c.2261T>C) pathogenic?

ANKRD50 p.Val754Ala (c.2261T>C) is classified Uncertain significance in ANKRD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely pathogenic (0.9152); Ultra-rare (popmax 0.0307%, afr).

How common is ANKRD50 p.Val754Ala (c.2261T>C) in the general population?

ANKRD50 p.Val754Ala (c.2261T>C) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about ANKRD50 p.Val754Ala (c.2261T>C)?

AlphaMissense predicts likely pathogenic (score 0.9152) — an in-silico prediction, not a clinical call.

ANKRD50 p.Val754Ala

c.2261T>C · VCV4640992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9152 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9152	likely pathogenic
REVEL	0.234	benign-leaning
SaProt	LLR -4.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 0.76, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 40 kb · p 3.5e-10 · regional, not allelic
Overall
CADD	24.8	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 0.0307% African / African-American · 23/74,894 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00143% 23/1,613,726 alleles · ultra-rare exomes 15/1,461,618 · genomes 8/152,108 · joint denominator

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: ANKRD50
Protein: p.Val754Ala
Coding: c.2261T>C
MANE Select: NM_020337
Type: single nucleotide variant
Location: chr4:124671016 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.26

Full ANKRD50 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD50 p.Ala1053Val Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala1081Gly Uncertain significance ★ same type
ANKRD50 p.Ala1201Ser Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala1277Val Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala219Asp Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala372Thr Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala437Val Uncertain significance ★ ⚠ same type
ANKRD50 p.Ala469Val Uncertain significance ★ ⚠ same type

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/ankrd50-p-val754ala (accessed [today's date]).

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