Is BLTP1 p.Ala1812Val (c.5435C>T) pathogenic?

BLTP1 p.Ala1812Val (c.5435C>T) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely benign (0.0742); Ultra-rare (popmax 0.0132%, sas).

How common is BLTP1 p.Ala1812Val (c.5435C>T) in the general population?

BLTP1 p.Ala1812Val (c.5435C>T) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about BLTP1 p.Ala1812Val (c.5435C>T)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

BLTP1 p.Ala1812Val

c.5435C>T · rs778731683 · VCV2556618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.055	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 2.2	GERP 2, phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 9,909 bp · p 0.01 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0132% South Asian · 12/91,052 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00103% 15/1,461,350 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,588
Remaining individualsnot grpmax-eligible	0.0048%	20,828

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.Ala1812Val
Coding: c.5435C>T
MANE Select: NM_001384125
dbSNP: rs778731683
Type: single nucleotide variant
Location: chr4:122247280 (GRCh38)
Residue 1812: 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-ala1812val (accessed [today's date]).

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