Is ANKRD50 p.Ser98Arg (c.294T>A) pathogenic?

ANKRD50 p.Ser98Arg (c.294T>A) is classified Uncertain significance in ANKRD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: ambiguous (0.5391); Very rare (popmax 0.00267%, afr).

How common is ANKRD50 p.Ser98Arg (c.294T>A) in the general population?

ANKRD50 p.Ser98Arg (c.294T>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ANKRD50 p.Ser98Arg (c.294T>A)?

AlphaMissense predicts ambiguous (score 0.5391) — an in-silico prediction, not a clinical call.

ANKRD50 p.Ser98Arg

c.294T>A · rs369331040 · VCV2522425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5391 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5391	ambiguous
REVEL	0.019	moderately benign-leaning
SaProt	LLR -9.48	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.13, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 40 kb · p 3.5e-10 · regional, not allelic
Overall
CADD	17.43	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 0.00267% African / African-American · 2/74,918 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,614,064 alleles · very rare exomes 17/1,461,894 · genomes 2/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,459
Admixed American	0.00167%	60,000
European (non-Finnish)	0.00136%	73,753

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.Ser98Arg
Coding: c.294T>A
MANE Select: NM_020337
dbSNP: rs369331040
Type: single nucleotide variant
Location: chr4:124710218 (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-ser98arg (accessed [today's date]).

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