Is ANKRD9 p.Ala280Ser (c.838G>T) pathogenic?

ANKRD9 p.Ala280Ser (c.838G>T) is classified Uncertain significance in ANKRD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.0998); Very rare (popmax 0.00807%, sas).

How common is ANKRD9 p.Ala280Ser (c.838G>T) in the general population?

ANKRD9 p.Ala280Ser (c.838G>T) is very rare (popmax 0.00807%, sas) (gnomAD).

What do computational predictors say about ANKRD9 p.Ala280Ser (c.838G>T)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

ANKRD9 p.Ala280Ser

c.838G>T · VCV3874170

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00807%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -5.29	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 0.7	GERP -1.9, phastCons 0.001
Regional constraint	o/e 1.04	unconstrained · MANE · 950 bp · p 0.42 · regional, not allelic
Overall
CADD	17.34	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 0.00807% South Asian · 7/86,726 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00265%

Overall 0.000564% 8/1,417,618 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00807%	12,389
African / African-American	0.00137%	73,080

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: ANKRD9
Protein: p.Ala280Ser
Coding: c.838G>T
MANE Select: NM_152326
Type: single nucleotide variant
Location: chr14:102507052 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.45

Full ANKRD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD9 p.Ala105Pro Uncertain significance ★ ⚠ same type
ANKRD9 p.Ala111Val Uncertain significance ★ ⚠ same type
ANKRD9 p.Ala12Val Uncertain significance ★ ⚠ same type
ANKRD9 p.Ala170Thr Uncertain significance ★ ⚠ same type
ANKRD9 p.Ala214Thr Uncertain significance ★ ⚠ same type
ANKRD9 p.Ala289Thr Uncertain significance ★ ⚠ same type
ANKRD9 p.Ala40Thr Uncertain significance ★ ⚠ same type
ANKRD9 p.Arg125Cys 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/ankrd9-p-ala280ser (accessed [today's date]).

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