Is ANKRD30A p.Ser1091Phe (c.3272C>T) pathogenic?

ANKRD30A p.Ser1091Phe (c.3272C>T) is classified Uncertain significance in ANKRD30A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.3339); Ultra-rare (popmax 0.0163%, nfe).

How common is ANKRD30A p.Ser1091Phe (c.3272C>T) in the general population?

ANKRD30A p.Ser1091Phe (c.3272C>T) is ultra-rare (popmax 0.0163%, nfe) (gnomAD).

What do computational predictors say about ANKRD30A p.Ser1091Phe (c.3272C>T)?

AlphaMissense predicts likely benign (score 0.3339) — an in-silico prediction, not a clinical call.

ANKRD30A p.Ser1091Phe

c.3272C>T · rs765402044 · VCV2358004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3339 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0163%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3339	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -8.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP 0.16
Regional constraint	o/e 1.13	unconstrained · MANE · 38 kb · p 0.00097 · regional, not allelic
Overall
CADD	16.22	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 0.0163% European (non-Finnish) · 190/1,163,460 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0124% 195/1,575,516 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0163%	6,123
Remaining individualsnot grpmax-eligible	0.0066%	15,147
African / African-American	0.00138%	72,436

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.Ser1091Phe
Coding: c.3272C>T
MANE Select: NM_052997
dbSNP: rs765402044
Type: single nucleotide variant
Location: chr10:37218984 (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-ser1091phe (accessed [today's date]).

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