Is ANKRD28 p.Pro305Ser (c.913C>T) pathogenic?

ANKRD28 p.Pro305Ser (c.913C>T) is classified Uncertain significance in ANKRD28 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely pathogenic (0.7279); Very rare (popmax 0.00988%, sas).

How common is ANKRD28 p.Pro305Ser (c.913C>T) in the general population?

ANKRD28 p.Pro305Ser (c.913C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about ANKRD28 p.Pro305Ser (c.913C>T)?

AlphaMissense predicts likely pathogenic (score 0.7279) — an in-silico prediction, not a clinical call.

ANKRD28 p.Pro305Ser

c.913C>T · rs747339688 · VCV3124832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7279 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7279	likely pathogenic
REVEL	0.653	pathogenic-leaning
SaProt	LLR -10.63	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 9.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 126 kb · p 1.2e-08 · regional, not allelic
Overall
CADD	29.1	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P275S vs ClinVar P305S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,074 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.000682% 11/1,613,884 alleles · very rare exomes 11/1,461,616 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,119
East Asian	0.00446%	22,432

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: ANKRD28
Protein: p.Pro305Ser
Coding: c.913C>T
MANE Select: NM_001349278
dbSNP: rs747339688
Type: single nucleotide variant
Location: chr3:15720998 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.91

Full ANKRD28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD28 p.Thr814Met Likely benign ★★ same type
ANKRD28 c.2562-2A>C Uncertain significance ★ same type
ANKRD28 p.Ala1029Val Uncertain significance ★ ⚠ same type
ANKRD28 p.Ala1044Ser Uncertain significance ★ ⚠ same type
ANKRD28 p.Ala119Thr Uncertain significance ★ ⚠ same type
ANKRD28 p.Ala146Gly Uncertain significance ★ ⚠ same type
ANKRD28 p.Ala244Val Uncertain significance ★ ⚠ same type
ANKRD28 p.Ala276Thr 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/ankrd28-p-pro305ser (accessed [today's date]).

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