Is BLTP1 p.Val1657Ala (c.4970T>C) pathogenic?

BLTP1 p.Val1657Ala (c.4970T>C) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely pathogenic (0.7018); Rare (popmax 0.121%, afr).

How common is BLTP1 p.Val1657Ala (c.4970T>C) in the general population?

BLTP1 p.Val1657Ala (c.4970T>C) is rare (popmax 0.121%, afr) (gnomAD).

What do computational predictors say about BLTP1 p.Val1657Ala (c.4970T>C)?

AlphaMissense predicts likely pathogenic (score 0.7018) — an in-silico prediction, not a clinical call.

BLTP1 p.Val1657Ala

c.4970T>C · VCV3261090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7018 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.7018	likely pathogenic
REVEL	0.288	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 9,909 bp · p 0.01 · regional, not allelic
Overall
CADD	23.6	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 0.121% African / African-American · 91/74,978 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0937%

Overall 0.00645% 104/1,612,602 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.121%	824
Admixed American	0.015%	6,650
Remaining individualsnot grpmax-eligible	0.0048%	20,813
European (non-Finnish)	8.48e-05%	1,179,092

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.Val1657Ala
Coding: c.4970T>C
MANE Select: NM_001384125
Type: single nucleotide variant
Location: chr4:122245073 (GRCh38)
Residue 1657: 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-val1657ala (accessed [today's date]).

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