Is BLTP2 p.Cys207Arg (c.619T>C) pathogenic?

BLTP2 p.Cys207Arg (c.619T>C) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1127); Rare (popmax 0.306%, afr).

How common is BLTP2 p.Cys207Arg (c.619T>C) in the general population?

BLTP2 p.Cys207Arg (c.619T>C) is rare (popmax 0.306%, afr) (gnomAD).

What do computational predictors say about BLTP2 p.Cys207Arg (c.619T>C)?

AlphaMissense predicts likely benign (score 0.1127) — an in-silico prediction, not a clinical call.

BLTP2 p.Cys207Arg

c.619T>C · VCV4213444

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1127 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.306%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1127	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 10 kb · p 0.6 · regional, not allelic
Overall
CADD	21.5	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 0.306% African / African-American · 230/75,056 alleles

Filtering AF 0.274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.261%

Overall 0.0155% 250/1,614,190 alleles · rare exomes 105/1,461,862 · genomes 145/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.306%	326
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.01%	10,005
South Asian	0.0011%	91,092
European (non-Finnish)	8.47e-05%	1,180,006

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: BLTP2
Protein: p.Cys207Arg
Coding: c.619T>C
MANE Select: NM_014680
Type: single nucleotide variant
Location: chr17:28642036 (GRCh38)
Structure: AlphaFold pLDDT 71.37

Full BLTP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/bltp2-p-cys207arg (accessed [today's date]).

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