Is BTN3A2 p.Asn77= (c.231C>T) pathogenic?

BTN3A2 p.Asn77= (c.231C>T) is classified Benign in BTN3A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-05). Common (popmax 27.1%, afr) — too common for a highly-penetrant pathogenic allele.

BTN3A2 p.Asn77=

Q: How common is BTN3A2 p.Asn77= (c.231C>T) in the general population?

BTN3A2 p.Asn77= (c.231C>T) is common (popmax 27.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.231C>T · rs28717012 · VCV770547

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 27.1%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.4
Overall
CADD	6.697	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.1% African / African-American · 20,068/73,970 alleles

Filtering AF 26.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.7%

Overall 23.8% 381,682/1,604,856 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	28.4%	4
African / African-Americangrpmax	27.1%	4
South Asian	25.3%	4
European (non-Finnish)	24.5%	4
Remaining individualsnot grpmax-eligible	23%	4
Ashkenazi Jewishnot grpmax-eligible	21.2%	5
Admixed American	21.2%	5
Middle Eastern	20.3%	5
Finnishnot grpmax-eligible	19.6%	5
East Asian	10.2%	10

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn77=
Coding: c.231C>T
MANE Select: NM_007047
dbSNP: rs28717012
Type: single nucleotide variant
Location: chr6:26368710 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.23 · 18 PDB
Residue 77: a disulfide bond; a β-strand; the ig-like v-type domain

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

Similar variants

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
BTN3A2 p.Ala48Thr 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-asn77 (accessed [today's date]).

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