Is BLTP1 p.Pro265Ser (c.793C>T) pathogenic?

BLTP1 p.Pro265Ser (c.793C>T) is classified Uncertain significance in BLTP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-03). AlphaMissense: likely pathogenic (0.6392); Ultra-rare (popmax 0.0173%, amr).

How common is BLTP1 p.Pro265Ser (c.793C>T) in the general population?

BLTP1 p.Pro265Ser (c.793C>T) is ultra-rare (popmax 0.0173%, amr) (gnomAD).

What do computational predictors say about BLTP1 p.Pro265Ser (c.793C>T)?

AlphaMissense predicts likely pathogenic (score 0.6392) — an in-silico prediction, not a clinical call.

BLTP1 p.Pro265Ser

c.793C>T · rs754477649 · VCV1307905

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6392 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, amr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.6392	likely pathogenic
REVEL	0.827	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 17 kb · p 0.0013 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0173% Admixed American · 8/46,198 alleles

Filtering AF 0.00852% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00625%

Overall 0.000914% 14/1,532,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0173%	5,775
Remaining individualsnot grpmax-eligible	0.00843%	11,869
African / African-American	0.00142%	70,302

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.Pro265Ser
Coding: c.793C>T
MANE Select: NM_001384125
dbSNP: rs754477649
Type: single nucleotide variant
Location: chr4:122188060 (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-pro265ser (accessed [today's date]).

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