Is ANKRD50 p.Ile252Val (c.754A>G) pathogenic?

ANKRD50 p.Ile252Val (c.754A>G) is classified Uncertain significance in ANKRD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: likely benign (0.2834); Ultra-rare (popmax 0.0752%, sas).

How common is ANKRD50 p.Ile252Val (c.754A>G) in the general population?

ANKRD50 p.Ile252Val (c.754A>G) is ultra-rare (popmax 0.0752%, sas) (gnomAD).

What do computational predictors say about ANKRD50 p.Ile252Val (c.754A>G)?

AlphaMissense predicts likely benign (score 0.2834) — an in-silico prediction, not a clinical call.

ANKRD50 p.Ile252Val

c.754A>G · VCV3297716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2834 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0752%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2834	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -8.49	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 6.2	GERP 2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 40 kb · p 3.5e-10 · regional, not allelic
Overall
CADD	21.5	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 0.0752% South Asian · 64/85,120 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.055%

Overall 0.00423% 67/1,584,662 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0752%	1,330
Remaining individualsnot grpmax-eligible	0.00326%	30,647
European (non-Finnish)	8.56e-05%	1,168,435

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.Ile252Val
Coding: c.754A>G
MANE Select: NM_020337
Type: single nucleotide variant
Location: chr4:124672523 (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-ile252val (accessed [today's date]).

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