Is BTN3A2 p.Ser327Trp (c.980C>G) pathogenic?

BTN3A2 p.Ser327Trp (c.980C>G) is classified Uncertain significance in BTN3A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely benign (0.1219); Ultra-rare (popmax 0.0148%, nfe).

How common is BTN3A2 p.Ser327Trp (c.980C>G) in the general population?

BTN3A2 p.Ser327Trp (c.980C>G) is ultra-rare (popmax 0.0148%, nfe) (gnomAD).

What do computational predictors say about BTN3A2 p.Ser327Trp (c.980C>G)?

AlphaMissense predicts likely benign (score 0.1219) — an in-silico prediction, not a clinical call.

BTN3A2 p.Ser327Trp

c.980C>G · rs542217150 · VCV3135539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1219 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1219	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -9.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.9	GERP -1.1
Regional constraint	o/e 0.88	unconstrained · MANE · 4,036 bp · p 0.061 · regional, not allelic
Overall
CADD	14.55	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 0.0148% European (non-Finnish) · 174/1,179,548 alleles

Filtering AF 0.0129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0123%

Overall 0.0113% 182/1,612,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0148%	6,779
Remaining individualsnot grpmax-eligible	0.00641%	15,605
African / African-American	0.00537%	18,638

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: BTN3A2
Protein: p.Ser327Trp
Coding: c.980C>G
MANE Select: NM_007047
dbSNP: rs542217150
Type: single nucleotide variant
Location: chr6:26374342 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23 · 18 PDB

Full BTN3A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTN3A2 p.Ser327= Benign ★ same residue
BTN3A2 p.Ala110Thr Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala182Asp Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala192Val Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala233Gly Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala245Thr Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala264Thr Uncertain significance ★ ⚠ same type
BTN3A2 p.Ala266Val 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/btn3a2-p-ser327trp (accessed [today's date]).

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