Is BATF2 p.Arg75Gln (c.224G>A) pathogenic?

BATF2 p.Arg75Gln (c.224G>A) is classified Likely benign in BATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.0698); Ultra-rare (popmax 0.0223%, eas).

How common is BATF2 p.Arg75Gln (c.224G>A) in the general population?

BATF2 p.Arg75Gln (c.224G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about BATF2 p.Arg75Gln (c.224G>A)?

AlphaMissense predicts likely benign (score 0.0698) — an in-silico prediction, not a clinical call.

BATF2 p.Arg75Gln

c.224G>A · VCV3989009

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0698 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0698	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -5.16	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 -5.5	GERP -3.2
Regional constraint	o/e 0.87	unconstrained · MANE · 7,782 bp · p 0.014 · regional, not allelic
Overall
CADD	0.755	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,880 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00136% 22/1,613,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,488
Remaining individualsnot grpmax-eligible	0.0032%	31,244
Admixed American	0.00167%	60,000
European (non-Finnish)	0.000763%	131,112

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.Arg75Gln
Coding: c.224G>A
MANE Select: NM_138456
Type: single nucleotide variant
Location: chr11:64989730 (GRCh38)
Gene constraint: LOEUF 1.522 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.92
Residue 75: the bzip domain

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

Similar variants

BATF2 p.Arg75Trp 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-arg75gln (accessed [today's date]).

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