Is ANKRD30A p.Pro635Thr (c.1903C>A) pathogenic?

ANKRD30A p.Pro635Thr (c.1903C>A) is classified Uncertain significance in ANKRD30A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: likely benign (0.0814); Very rare (popmax 0.000254%, nfe).

How common is ANKRD30A p.Pro635Thr (c.1903C>A) in the general population?

ANKRD30A p.Pro635Thr (c.1903C>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ANKRD30A p.Pro635Thr (c.1903C>A)?

AlphaMissense predicts likely benign (score 0.0814) — an in-silico prediction, not a clinical call.

ANKRD30A p.Pro635Thr

c.1903C>A · rs1250795090 · VCV2219479

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.3	GERP -3.3
Regional constraint	o/e 1.10	unconstrained · MANE · 39 kb · p 0.0028 · regional, not allelic
Overall
CADD	0.553	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000254% European (non-Finnish) · 3/1,179,728 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,611,954 alleles · very rare

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: ANKRD30A
Protein: p.Pro635Thr
Coding: c.1903C>A
MANE Select: NM_052997
dbSNP: rs1250795090
Type: single nucleotide variant
Location: chr10:37162651 (GRCh38)
Gene constraint: LOEUF 1.295 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.16 · 1 PDB

Full ANKRD30A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD30A p.Ala1006Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1119Gly Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala120Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1226Glu Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala122Val Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1273Gly Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala1298Ser Uncertain significance ★ ⚠ same type
ANKRD30A p.Ala146Thr 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/ankrd30a-p-pro635thr (accessed [today's date]).

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