Is BLTP1 p.Arg638Cys (c.1912C>T) pathogenic?

BLTP1 p.Arg638Cys (c.1912C>T) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). AlphaMissense: ambiguous (0.522); Ultra-rare (popmax 0.0198%, sas).

How common is BLTP1 p.Arg638Cys (c.1912C>T) in the general population?

BLTP1 p.Arg638Cys (c.1912C>T) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

What do computational predictors say about BLTP1 p.Arg638Cys (c.1912C>T)?

AlphaMissense predicts ambiguous (score 0.522) — an in-silico prediction, not a clinical call.

BLTP1 p.Arg638Cys

c.1912C>T · VCV4212965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.522 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Computational evidence

Protein change
AlphaMissense	0.522	ambiguous
REVEL	0.311	indeterminate
Splicing
SpliceAI	Δ0.21	donor loss · deltas
Constraint at this position
Conservation	phyloP 1.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 45 kb · p 1e-08 · regional, not allelic
Overall
CADD	23.9	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 0.0198% South Asian · 18/90,868 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00219% 32/1,459,600 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,048
Admixed American	0.00335%	29,889
Remaining individualsnot grpmax-eligible	0.00321%	31,186
East Asian	0.00224%	44,682
European (non-Finnish)	0.000763%	130,991

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.Arg638Cys
Coding: c.1912C>T
MANE Select: NM_001384125
Type: single nucleotide variant
Location: chr4:122209318 (GRCh38)
Residue 638: 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.Arg638His Uncertain significance ★★ ⚠ same residue
BLTP1 p.Arg638= Likely benign ★ same residue
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

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-arg638cys (accessed [today's date]).

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