Is BTN2A2 p.Pro479Ser (c.1435C>T) pathogenic?

BTN2A2 p.Pro479Ser (c.1435C>T) is classified Benign in BTN2A2 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-01-03). AlphaMissense: likely benign (0.1263); Common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BTN2A2 p.Pro479Ser (c.1435C>T)?

AlphaMissense predicts likely benign (score 0.1263) — an in-silico prediction, not a clinical call.

BTN2A2 p.Pro479Ser

Q: How common is BTN2A2 p.Pro479Ser (c.1435C>T) in the general population?

BTN2A2 p.Pro479Ser (c.1435C>T) is common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1435C>T · rs16891646 · VCV778227

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1263 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1263	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -8.79	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 0.98	GERP 0.85, phastCons 0.28
Regional constraint	o/e 0.94	unconstrained · MANE · 9,142 bp · p 0.12 · regional, not allelic
Overall
CADD	18.57	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 6.53% African / African-American · 4,899/75,018 alleles

Filtering AF 6.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.32%

Overall 0.506% 8,163/1,614,182 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.53%	15
Ashkenazi Jewishnot grpmax-eligible	2.23%	45
Middle Eastern	1.19%	84
Amishnot grpmax-eligible	1.1%	91
Remaining individualsnot grpmax-eligible	0.768%	130
Admixed American	0.711%	141
South Asian	0.326%	307
European (non-Finnish)	0.111%	901
East Asian	0.00891%	11,221
Finnishnot grpmax-eligible	0.00781%	12,808

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: BTN2A2
Protein: p.Pro479Ser
Coding: c.1435C>T
MANE Select: NM_006995
dbSNP: rs16891646
Type: single nucleotide variant
Location: chr6:26392830 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.50 · 1 PDB
Residue 479: a UniProt-annotated variant site (in); the b30.2/spry domain

Full BTN2A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTN2A2 p.Ala147Gly Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala199Thr Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala201Pro Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala210Ser Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala248Glu Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala248Pro Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala254Thr Uncertain significance ★ ⚠ same type
BTN2A2 p.Ala327Val 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/btn2a2-p-pro479ser (accessed [today's date]).

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