Is BATF2 p.Pro226Ala (c.676C>G) pathogenic?

BATF2 p.Pro226Ala (c.676C>G) is classified Uncertain significance in BATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0721); Ultra-rare (popmax 0.0137%, amr).

How common is BATF2 p.Pro226Ala (c.676C>G) in the general population?

BATF2 p.Pro226Ala (c.676C>G) is ultra-rare (popmax 0.0137%, amr) (gnomAD).

What do computational predictors say about BATF2 p.Pro226Ala (c.676C>G)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

BATF2 p.Pro226Ala

c.676C>G · VCV4645210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.76	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 0.72	GERP -3.1, phastCons 0.001
Regional constraint	o/e 0.87	unconstrained · MANE · 7,782 bp · p 0.014 · regional, not allelic
Overall
CADD	0.914	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 0.0137% Admixed American · 8/58,484 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00493%

Overall 0.000999% 16/1,600,906 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0137%	7,310
East Asian	0.00447%	22,381
Ashkenazi Jewishnot grpmax-eligible	0.00351%	28,510
South Asian	0.00223%	44,765
African / African-American	0.00134%	74,616
European (non-Finnish)	0.000171%	586,356

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: BATF2
Protein: p.Pro226Ala
Coding: c.676C>G
MANE Select: NM_138456
Type: single nucleotide variant
Location: chr11:64989278 (GRCh38)
Gene constraint: LOEUF 1.522 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.92
Residue 226: the 'disordered' region

Full BATF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BATF2 p.Pro226Ser Uncertain significance ★ ⚠ same residue
BATF2 c.40-2A>T Uncertain significance ★ same type
BATF2 p.Ala178Asp Uncertain significance ★ ⚠ same type
BATF2 p.Ala29Val Uncertain significance ★ ⚠ same type
BATF2 p.Ala31Thr Uncertain significance ★ ⚠ same type
BATF2 p.Arg28Gln Uncertain significance ★ ⚠ same type
BATF2 p.Arg28Trp Uncertain significance ★ ⚠ same type
BATF2 p.Arg33Gln 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/batf2-p-pro226ala (accessed [today's date]).

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