Is ANKRD30A p.Ser640Ala (c.1918T>G) pathogenic?

ANKRD30A p.Ser640Ala (c.1918T>G) is classified Uncertain significance in ANKRD30A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.00534%, afr).

How common is ANKRD30A p.Ser640Ala (c.1918T>G) in the general population?

ANKRD30A p.Ser640Ala (c.1918T>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ANKRD30A p.Ser640Ala (c.1918T>G)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

ANKRD30A p.Ser640Ala

c.1918T>G · VCV4105850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -11.10	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 -6.5	GERP -3.3
Regional constraint	o/e 1.10	unconstrained · MANE · 39 kb · p 0.0028 · regional, not allelic
Overall
CADD	3.417	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 0.00534% African / African-American · 4/74,858 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00263% 4/152,164 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.Ser640Ala
Coding: c.1918T>G
MANE Select: NM_052997
Type: single nucleotide variant
Location: chr10:37162666 (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-ser640ala (accessed [today's date]).

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