Is BLTP1 p.Met95Val (c.283A>G) pathogenic?

BLTP1 p.Met95Val (c.283A>G) is classified Conflicting classifications of pathogenicity in BLTP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-28). AlphaMissense: likely benign (0.0975); Ultra-rare (popmax 0.0235%, amr).

How common is BLTP1 p.Met95Val (c.283A>G) in the general population?

BLTP1 p.Met95Val (c.283A>G) is ultra-rare (popmax 0.0235%, amr) (gnomAD).

What do computational predictors say about BLTP1 p.Met95Val (c.283A>G)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

BLTP1 p.Met95Val

c.283A>G · rs199640893 · VCV1338126

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0235%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.17	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP -1.2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 17 kb · p 0.0013 · regional, not allelic
Overall
CADD	17.45	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 0.0235% Admixed American · 14/59,512 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.00807% 129/1,597,574 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0235%	4,251
European (non-Finnish)	0.00934%	10,702
Remaining individualsnot grpmax-eligible	0.00808%	12,381
South Asian	0.00111%	90,320

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: BLTP1
Protein: p.Met95Val
Coding: c.283A>G
MANE Select: NM_001384125
dbSNP: rs199640893
Type: single nucleotide variant
Location: chr4:122174642 (GRCh38)

Full BLTP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP1 p.Arg968Cys Likely pathogenic ★★ ⚠ same type
BLTP1 c.1498+4A>G Uncertain significance ★★ same type
BLTP1 p.Ala2332Thr Uncertain significance ★★ ⚠ same type
BLTP1 p.Arg1317His Uncertain significance ★★ same type
BLTP1 p.Arg1791Lys Uncertain significance ★★ ⚠ same type
BLTP1 p.Arg2095His Uncertain significance ★★ same type
BLTP1 p.Arg2279Cys Uncertain significance ★★ same type
BLTP1 p.Arg3665Gln 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/bltp1-p-met95val (accessed [today's date]).

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