Is BTN3A1 p.Phe128Ser (c.383T>C) pathogenic?

BTN3A1 p.Phe128Ser (c.383T>C) is classified Uncertain significance in BTN3A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely pathogenic (0.9049); Very rare (popmax 0.00327%, afr).

How common is BTN3A1 p.Phe128Ser (c.383T>C) in the general population?

BTN3A1 p.Phe128Ser (c.383T>C) is very rare (popmax 0.00327%, afr) (gnomAD).

What do computational predictors say about BTN3A1 p.Phe128Ser (c.383T>C)?

AlphaMissense predicts likely pathogenic (score 0.9049) — an in-silico prediction, not a clinical call.

BTN3A1 p.Phe128Ser

c.383T>C · rs1461205077 · VCV2529118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9049 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00327%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9049	likely pathogenic · top 4% in BTN3A1
REVEL	0.157	moderately benign-leaning
SaProt	LLR -13.86	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 1,627 bp · p 2.8e-05 · regional, not allelic
Overall
CADD	24.7	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 0.00327% African / African-American · 2/61,190 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000203%

Overall 0.00021% 3/1,430,366 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00327%	30,595
European (non-Finnish)	9.54e-05%	1,048,024

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: BTN3A1
Protein: p.Phe128Ser
Coding: c.383T>C
MANE Select: NM_007048
dbSNP: rs1461205077
Type: single nucleotide variant
Location: chr6:26406206 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.66 · 44 PDB
Residue 128: a β-strand; the ig-like v-type 1 domain

Full BTN3A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTN3A1 p.Leu227His Likely benign ★★ ⚠ same type
BTN3A1 p.Ala251Ser Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala251Thr Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala294Ser Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala340Val Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala48Thr Uncertain significance ★ ⚠ same type
BTN3A1 p.Ala91Thr Uncertain significance ★ ⚠ same type
BTN3A1 p.Arg101Trp 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/btn3a1-p-phe128ser (accessed [today's date]).

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