Is BTNL8 p.Pro79Ser (c.235C>T) pathogenic?

BTNL8 p.Pro79Ser (c.235C>T) is classified Uncertain significance in BTNL8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-20). AlphaMissense: likely benign (0.1305); Very rare (popmax 0.0011%, sas).

How common is BTNL8 p.Pro79Ser (c.235C>T) in the general population?

BTNL8 p.Pro79Ser (c.235C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BTNL8 p.Pro79Ser (c.235C>T)?

AlphaMissense predicts likely benign (score 0.1305) — an in-silico prediction, not a clinical call.

BTNL8 p.Pro79Ser

c.235C>T · rs367763125 · VCV2619634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1305 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1305	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -7.47	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 -5.5	GERP -3.7
Regional constraint	o/e 1.08	unconstrained · MANE · 48 kb · p 0.16 · regional, not allelic
Overall
CADD	13.83	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 0.0011% South Asian · 1/91,084 alleles

Overall 6.84e-05% 1/1,461,890 alleles · very rare

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: BTNL8
Protein: p.Pro79Ser
Coding: c.235C>T
MANE Select: NM_001040462
dbSNP: rs367763125
Type: single nucleotide variant
Location: chr5:180908771 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.68 · 1 PDB
Residue 79: a disulfide bond; the ig-like v-type 1 domain

Full BTNL8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTNL8 p.Ala267= Likely benign ★★ same type
BTNL8 p.Ala211Val Uncertain significance ★ ⚠ same type
BTNL8 p.Ala283Thr Uncertain significance ★ ⚠ same type
BTNL8 p.Ala475Thr Uncertain significance ★ ⚠ same type
BTNL8 p.Ala50Pro Uncertain significance ★ ⚠ same type
BTNL8 p.Ala93Val Uncertain significance ★ ⚠ same type
BTNL8 p.Arg162Gly Uncertain significance ★ ⚠ same type
BTNL8 p.Arg162Trp 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/btnl8-p-pro79ser (accessed [today's date]).

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