Is ANKRD24 p.Arg822Pro (c.2465G>C) pathogenic?

ANKRD24 p.Arg822Pro (c.2465G>C) is classified Uncertain significance in ANKRD24 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: ambiguous (0.3459); Ultra-rare (popmax 0.0628%, eas).

How common is ANKRD24 p.Arg822Pro (c.2465G>C) in the general population?

ANKRD24 p.Arg822Pro (c.2465G>C) is ultra-rare (popmax 0.0628%, eas) (gnomAD).

What do computational predictors say about ANKRD24 p.Arg822Pro (c.2465G>C)?

AlphaMissense predicts ambiguous (score 0.3459) — an in-silico prediction, not a clinical call.

ANKRD24 p.Arg822Pro

c.2465G>C · VCV4640762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3459 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0628%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3459	ambiguous
REVEL	0.157	moderately benign-leaning
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 38 kb · p 0.05 · regional, not allelic
Overall
CADD	18.85	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 0.0628% East Asian · 19/30,268 alleles

Filtering AF 0.041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0341%

Overall 0.00148% 19/1,287,180 alleles · ultra-rare exomes 18/1,135,518 · genomes 1/151,662 · 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: ANKRD24
Protein: p.Arg822Pro
Coding: c.2465G>C
MANE Select: NM_001393985
Type: single nucleotide variant
Location: chr19:4217625 (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.Arg822Gln Uncertain significance ★ ⚠ same residue
ANKRD24 p.Arg822Gly Uncertain significance ★ ⚠ same residue
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

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-arg822pro (accessed [today's date]).

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