Is ANKRD52 p.Ala49Val (c.146C>T) pathogenic?

ANKRD52 p.Ala49Val (c.146C>T) is classified Uncertain significance in ANKRD52 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely pathogenic (0.8874); Very rare (popmax 0.00804%, afr).

How common is ANKRD52 p.Ala49Val (c.146C>T) in the general population?

ANKRD52 p.Ala49Val (c.146C>T) is very rare (popmax 0.00804%, afr) (gnomAD).

What do computational predictors say about ANKRD52 p.Ala49Val (c.146C>T)?

AlphaMissense predicts likely pathogenic (score 0.8874) — an in-silico prediction, not a clinical call.

ANKRD52 p.Ala49Val

c.146C>T · VCV4108001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00804%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8874	likely pathogenic
REVEL	0.518	indeterminate
SaProt	LLR -9.88	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 5,981 bp · p 4.6e-37 · regional, not allelic
Overall
CADD	29.5	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 0.00804% African / African-American · 6/74,590 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00363% 58/1,596,964 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00804%	12,432
European (non-Finnish)	0.00427%	23,439
Admixed American	0.00175%	57,192
Remaining individualsnot grpmax-eligible	0.00161%	61,942

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.Ala49Val
Coding: c.146C>T
MANE Select: NM_173595
Type: single nucleotide variant
Location: chr12:56257327 (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-ala49val (accessed [today's date]).

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