Is BLTP1 p.Val640Ile (c.1918G>A) pathogenic?

BLTP1 p.Val640Ile (c.1918G>A) is classified Likely benign in BLTP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-05-01). AlphaMissense: likely benign (0.0534); Rare (popmax 0.565%, afr).

How common is BLTP1 p.Val640Ile (c.1918G>A) in the general population?

BLTP1 p.Val640Ile (c.1918G>A) is rare (popmax 0.565%, afr) (gnomAD).

What do computational predictors say about BLTP1 p.Val640Ile (c.1918G>A)?

AlphaMissense predicts likely benign (score 0.0534) — an in-silico prediction, not a clinical call.

BLTP1 p.Val640Ile

c.1918G>A · rs72925924 · VCV2655064

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0534 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.565%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0534	likely benign
REVEL	0.043	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 0.27	GERP -5.1, phastCons 0.003
Regional constraint	o/e 0.82	unconstrained · MANE · 45 kb · p 1e-08 · regional, not allelic
Overall
CADD	13.15	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 0.565% African / African-American · 423/74,816 alleles

Filtering AF 0.521% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.503%

Overall 0.0386% 623/1,611,902 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.565%	177
Admixed American	0.082%	1,220
Remaining individualsnot grpmax-eligible	0.0577%	1,732
Middle Eastern	0.0502%	1,993
East Asian	0.0179%	5,588
European (non-Finnish)	0.0084%	11,909
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,768
South Asian	0.0033%	30,292

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.Val640Ile
Coding: c.1918G>A
MANE Select: NM_001384125
dbSNP: rs72925924
Type: single nucleotide variant
Location: chr4:122209324 (GRCh38)
Residue 640: a UniProt-annotated variant site (in alkkucs)

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-val640ile (accessed [today's date]).

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