Is BLTP1 p.Arg2222Trp (c.6664C>T) pathogenic?

BLTP1 p.Arg2222Trp (c.6664C>T) is classified Benign in BLTP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-04). AlphaMissense: likely benign (0.2113); Common (popmax 5.43%, nfe) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BLTP1 p.Arg2222Trp (c.6664C>T)?

AlphaMissense predicts likely benign (score 0.2113) — an in-silico prediction, not a clinical call.

BLTP1 p.Arg2222Trp

Q: How common is BLTP1 p.Arg2222Trp (c.6664C>T) in the general population?

BLTP1 p.Arg2222Trp (c.6664C>T) is common (popmax 5.43%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6664C>T · rs45510500 · VCV1241877

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2113 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.43%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2113	likely benign
REVEL	0.172	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 4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 21 kb · p 3.1e-07 · 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 5.43% European (non-Finnish) · 64,079/1,179,592 alleles

Filtering AF 5.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.38%

Overall 4.48% 72,301/1,613,564 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	5.43%	18
Finnishnot grpmax-eligible	4.97%	20
Remaining individualsnot grpmax-eligible	3.4%	29
Admixed American	1.84%	54
Amishnot grpmax-eligible	1.43%	70
Ashkenazi Jewishnot grpmax-eligible	1.35%	74
Middle Eastern	1.06%	95
South Asian	0.809%	124
African / African-American	0.787%	127
East Asian	0.0201%	4,983

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.Arg2222Trp
Coding: c.6664C>T
MANE Select: NM_001384125
dbSNP: rs45510500
Type: single nucleotide variant
Location: chr4:122258745 (GRCh38)
Residue 2222: 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-arg2222trp (accessed [today's date]).

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