Is ANKRD29 p.Ala185Pro (c.553G>C) pathogenic?

ANKRD29 p.Ala185Pro (c.553G>C) is classified Uncertain significance in ANKRD29 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely pathogenic (0.9826); Very rare (popmax 0.00663%, sas).

How common is ANKRD29 p.Ala185Pro (c.553G>C) in the general population?

ANKRD29 p.Ala185Pro (c.553G>C) is very rare (popmax 0.00663%, sas) (gnomAD).

What do computational predictors say about ANKRD29 p.Ala185Pro (c.553G>C)?

AlphaMissense predicts likely pathogenic (score 0.9826) — an in-silico prediction, not a clinical call.

ANKRD29 p.Ala185Pro

c.553G>C · rs763706312 · VCV2303678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00663%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9826	likely pathogenic · top 2% in ANKRD29
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -16.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 62 kb · p 0.28 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00663% South Asian · 6/90,510 alleles

Filtering AF 0.00288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.00069% 11/1,595,302 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00663%	15,085
European (non-Finnish)	0.000424%	235,667

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: ANKRD29
Protein: p.Ala185Pro
Coding: c.553G>C
MANE Select: NM_173505
dbSNP: rs763706312
Type: single nucleotide variant
Location: chr18:23619605 (GRCh38)
Gene constraint: LOEUF 1.187 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.86

Full ANKRD29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD29 p.Ala103Thr Uncertain significance ★ same type
ANKRD29 p.Ala202Val Uncertain significance ★ same type
ANKRD29 p.Ala249Val Uncertain significance ★ ⚠ same type
ANKRD29 p.Ala260Val Uncertain significance ★ ⚠ same type
ANKRD29 p.Ala280Thr Uncertain significance ★ ⚠ same type
ANKRD29 p.Ala280Val Uncertain significance ★ ⚠ same type
ANKRD29 p.Arg200Gly Uncertain significance ★ same type
ANKRD29 p.Arg204His 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/ankrd29-p-ala185pro (accessed [today's date]).

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