Is ANKRD30A p.Ser153Pro (c.457T>C) pathogenic?

ANKRD30A p.Ser153Pro (c.457T>C) is classified Uncertain significance in ANKRD30A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). AlphaMissense: likely benign (0.1039); Very rare (popmax 0.000428%, nfe).

How common is ANKRD30A p.Ser153Pro (c.457T>C) in the general population?

ANKRD30A p.Ser153Pro (c.457T>C) is very rare (popmax 0.000428%, nfe) (gnomAD).

What do computational predictors say about ANKRD30A p.Ser153Pro (c.457T>C)?

AlphaMissense predicts likely benign (score 0.1039) — an in-silico prediction, not a clinical call.

ANKRD30A p.Ser153Pro

c.457T>C · rs1211251186 · VCV2483729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1039 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000428%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1039	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -7.61	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 -4.3	GERP -3.7
Regional constraint	o/e 1.10	unconstrained · MANE · 39 kb · p 0.0028 · regional, not allelic
Overall
CADD	6.041	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 0.000428% European (non-Finnish) · 5/1,167,848 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.00113% 18/1,587,818 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0379%	2,641
Remaining individualsnot grpmax-eligible	0.00327%	30,617
European (non-Finnish)grpmax	0.000428%	233,570

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser153Pro
Coding: c.457T>C
MANE Select: NM_052997
dbSNP: rs1211251186
Type: single nucleotide variant
Location: chr10:37130325 (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-ser153pro (accessed [today's date]).

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