Is ANKRD52 p.Arg892His (c.2675G>A) pathogenic?

ANKRD52 p.Arg892His (c.2675G>A) is classified Uncertain significance in ANKRD52 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: likely benign (0.1181); Ultra-rare (popmax 0.0201%, nfe).

How common is ANKRD52 p.Arg892His (c.2675G>A) in the general population?

ANKRD52 p.Arg892His (c.2675G>A) is ultra-rare (popmax 0.0201%, nfe) (gnomAD).

What do computational predictors say about ANKRD52 p.Arg892His (c.2675G>A)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

ANKRD52 p.Arg892His

c.2675G>A · rs201659742 · VCV2365871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -10.07	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -0.26, phastCons 0.98
Regional constraint	o/e 0.68	unconstrained · MANE · 9,142 bp · p 1.1e-19 · regional, not allelic
Overall
CADD	22.2	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 0.0201% European (non-Finnish) · 237/1,179,916 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.016% 258/1,613,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0201%	4,979
African / African-American	0.0107%	9,367
Remaining individualsnot grpmax-eligible	0.008%	12,492
South Asian	0.00768%	13,013
Admixed American	0.00167%	59,998

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: ANKRD52
Protein: p.Arg892His
Coding: c.2675G>A
MANE Select: NM_173595
dbSNP: rs201659742
Type: single nucleotide variant
Location: chr12:56244699 (GRCh38)
Gene constraint: LOEUF 0.122 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.71

Full ANKRD52 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD52 c.694-3C>T Benign ★★ same type
ANKRD52 p.Asn466= Benign ★★ same type
ANKRD52 p.Ala102Ser Uncertain significance ★ ⚠ same type
ANKRD52 p.Ala1041Val Uncertain significance ★ ⚠ same type
ANKRD52 p.Ala1043Thr Uncertain significance ★ ⚠ same type
ANKRD52 p.Ala1051Thr Uncertain significance ★ ⚠ same type
ANKRD52 p.Ala1067Thr Uncertain significance ★ ⚠ same type
ANKRD52 p.Ala215Val 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/ankrd52-p-arg892his (accessed [today's date]).

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