Is BLTP1 p.Pro114Ser (c.340C>T) pathogenic?

BLTP1 p.Pro114Ser (c.340C>T) is classified Uncertain significance in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.6819); Ultra-rare (popmax 0.0513%, mid).

How common is BLTP1 p.Pro114Ser (c.340C>T) in the general population?

BLTP1 p.Pro114Ser (c.340C>T) is ultra-rare (popmax 0.0513%, mid) (gnomAD).

What do computational predictors say about BLTP1 p.Pro114Ser (c.340C>T)?

AlphaMissense predicts likely pathogenic (score 0.6819) — an in-silico prediction, not a clinical call.

BLTP1 p.Pro114Ser

c.340C>T · VCV4212886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6819 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, mid)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.6819	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 17 kb · p 0.0013 · regional, not allelic
Overall
CADD	24.1	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 0.0513% Middle Eastern · 3/5,852 alleles

Filtering AF 0.0139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00744%

Overall 0.00151% 23/1,522,334 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0513%	1,951
Admixed American	0.00338%	29,549
Remaining individualsnot grpmax-eligible	0.00337%	29,640
European (non-Finnish)	0.00145%	68,751

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.Pro114Ser
Coding: c.340C>T
MANE Select: NM_001384125
Type: single nucleotide variant
Location: chr4:122175896 (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-pro114ser (accessed [today's date]).

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