Is BATF2 p.Arg28Trp (c.82C>T) pathogenic?

BATF2 p.Arg28Trp (c.82C>T) is classified Uncertain significance in BATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.6782); Very rare (popmax 0.00366%, nfe).

How common is BATF2 p.Arg28Trp (c.82C>T) in the general population?

BATF2 p.Arg28Trp (c.82C>T) is very rare (popmax 0.00366%, nfe) (gnomAD).

What do computational predictors say about BATF2 p.Arg28Trp (c.82C>T)?

AlphaMissense predicts likely pathogenic (score 0.6782) — an in-silico prediction, not a clinical call.

BATF2 p.Arg28Trp

c.82C>T · rs749340007 · VCV2618345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6782 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00366%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6782	likely pathogenic
REVEL	0.549	indeterminate
SaProt	LLR -12.23	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 7,782 bp · p 0.014 · regional, not allelic
Overall
CADD	29.4	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00366% European (non-Finnish) · 43/1,175,462 alleles

Filtering AF 0.00276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00293% 47/1,604,086 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00366%	27,336
Remaining individualsnot grpmax-eligible	0.00161%	62,096
Finnishnot grpmax-eligible	0.00158%	63,240
African / African-American	0.00134%	74,770
South Asian	0.00112%	89,304

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.Arg28Trp
Coding: c.82C>T
MANE Select: NM_138456
dbSNP: rs749340007
Type: single nucleotide variant
Location: chr11:64994507 (GRCh38)
Gene constraint: LOEUF 1.522 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.92
Residue 28: the bzip domain; the 'disordered' region; the 'basic motif' region

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

Similar variants

BATF2 p.Arg28Gln 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.Arg33Gln Uncertain significance ★ same type
BATF2 p.Arg75Trp Uncertain significance ★ ⚠ same type
BATF2 p.Arg82His 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-arg28trp (accessed [today's date]).

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