Is BATF2 p.Pro127Leu (c.380C>T) pathogenic?

BATF2 p.Pro127Leu (c.380C>T) is classified Uncertain significance in BATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely benign (0.1171); Ultra-rare (popmax 0.019%, sas).

How common is BATF2 p.Pro127Leu (c.380C>T) in the general population?

BATF2 p.Pro127Leu (c.380C>T) is ultra-rare (popmax 0.019%, sas) (gnomAD).

What do computational predictors say about BATF2 p.Pro127Leu (c.380C>T)?

AlphaMissense predicts likely benign (score 0.1171) — an in-silico prediction, not a clinical call.

BATF2 p.Pro127Leu

c.380C>T · VCV3989019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1171 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1171	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.52	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 1.3	GERP -3.1, phastCons 0.15
Regional constraint	o/e 0.87	unconstrained · MANE · 7,782 bp · p 0.014 · regional, not allelic
Overall
CADD	13.99	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 0.019% South Asian · 17/89,302 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00994%

Overall 0.00333% 53/1,592,256 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.019%	5,253
European (non-Finnish)	0.00273%	36,565
African / African-American	0.00269%	37,185
Admixed American	0.00181%	55,398
Remaining individualsnot grpmax-eligible	0.00162%	61,692

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.Pro127Leu
Coding: c.380C>T
MANE Select: NM_138456
Type: single nucleotide variant
Location: chr11:64989574 (GRCh38)
Gene constraint: LOEUF 1.522 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 62.92

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-pro127leu (accessed [today's date]).

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