Is BATF2 p.Pro140Ser (c.418C>T) pathogenic?

BATF2 p.Pro140Ser (c.418C>T) is classified Uncertain significance in BATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.0873); Very rare (popmax 0.00228%, eas).

How common is BATF2 p.Pro140Ser (c.418C>T) in the general population?

BATF2 p.Pro140Ser (c.418C>T) is very rare (popmax 0.00228%, eas) (gnomAD).

What do computational predictors say about BATF2 p.Pro140Ser (c.418C>T)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

BATF2 p.Pro140Ser

c.418C>T · rs776116800 · VCV3133013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00228%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -6.12	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 4.8	GERP 0.46, phastCons 0.94
Regional constraint	o/e 0.87	unconstrained · MANE · 7,782 bp · p 0.014 · regional, not allelic
Overall
CADD	18.4	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 0.00228% East Asian · 1/43,790 alleles

Overall 0.000126% 2/1,592,292 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00228%	43,790
European (non-Finnish)	8.55e-05%	1,169,570

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.Pro140Ser
Coding: c.418C>T
MANE Select: NM_138456
dbSNP: rs776116800
Type: single nucleotide variant
Location: chr11:64989536 (GRCh38)
Gene constraint: LOEUF 1.522 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.92
Residue 140: the 'disordered' region

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

Similar variants

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
BATF2 p.Arg75Trp 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-pro140ser (accessed [today's date]).

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