Is ANKRD24 p.Arg765Pro (c.2294G>C) pathogenic?

ANKRD24 p.Arg765Pro (c.2294G>C) is classified Uncertain significance in ANKRD24 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: ambiguous (0.4032); Ultra-rare (popmax 0.0544%, eas).

How common is ANKRD24 p.Arg765Pro (c.2294G>C) in the general population?

ANKRD24 p.Arg765Pro (c.2294G>C) is ultra-rare (popmax 0.0544%, eas) (gnomAD).

What do computational predictors say about ANKRD24 p.Arg765Pro (c.2294G>C)?

AlphaMissense predicts ambiguous (score 0.4032) — an in-silico prediction, not a clinical call.

ANKRD24 p.Arg765Pro

c.2294G>C · rs765582446 · VCV2343569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4032 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0544%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4032	ambiguous
REVEL	0.036	moderately benign-leaning
SaProt	LLR -17.03	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.043, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 38 kb · p 0.05 · regional, not allelic
Overall
CADD	20.1	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 0.0544% East Asian · 22/40,452 alleles

Filtering AF 0.0367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.031%

Overall 0.00159% 24/1,512,820 alleles · ultra-rare exomes 21/1,360,816 · genomes 3/152,004 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0544%	1,839
Remaining individualsnot grpmax-eligible	0.00343%	29,143

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: ANKRD24
Protein: p.Arg765Pro
Coding: c.2294G>C
MANE Select: NM_001393985
dbSNP: rs765582446
Type: single nucleotide variant
Location: chr19:4217454 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.30

Full ANKRD24 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD24 p.Val1108Met Uncertain significance ★★ ⚠ same type
ANKRD24 p.Ala1015Thr Uncertain significance ★ ⚠ same type
ANKRD24 p.Ala1034Thr Uncertain significance ★ ⚠ same type
ANKRD24 p.Ala1040Asp Uncertain significance ★ ⚠ same type
ANKRD24 p.Ala1040Val Uncertain significance ★ ⚠ same type
ANKRD24 p.Ala1047Thr Uncertain significance ★ ⚠ same type
ANKRD24 p.Ala1077Val Uncertain significance ★ ⚠ same type
ANKRD24 p.Ala1102Val 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/ankrd24-p-arg765pro (accessed [today's date]).

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