Is BLTP3A p.Arg427Trp (c.1279C>T) pathogenic?

BLTP3A p.Arg427Trp (c.1279C>T) is classified Uncertain significance in BLTP3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.0838); Ultra-rare (popmax 0.035%, amr).

How common is BLTP3A p.Arg427Trp (c.1279C>T) in the general population?

BLTP3A p.Arg427Trp (c.1279C>T) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about BLTP3A p.Arg427Trp (c.1279C>T)?

AlphaMissense predicts likely benign (score 0.0838) — an in-silico prediction, not a clinical call.

BLTP3A p.Arg427Trp

c.1279C>T · VCV3481036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0838 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0838	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -9.06	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 0.17	GERP 0.72, phastCons 0.2
Regional constraint	o/e 0.88	unconstrained · MANE · 80 kb · p 4.8e-07 · regional, not allelic
Overall
CADD	20.4	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 0.035% Admixed American · 21/59,974 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00273% 44/1,613,884 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,856
South Asian	0.00879%	11,379
African / African-American	0.008%	12,502
Finnishnot grpmax-eligible	0.00156%	64,026
European (non-Finnish)	0.000678%	147,488

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: BLTP3A
Protein: p.Arg427Trp
Coding: c.1279C>T
MANE Select: NM_017754
Type: single nucleotide variant
Location: chr6:34856397 (GRCh38)
Structure: AlphaFold pLDDT 67.37

Full BLTP3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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BLTP3A p.Ala1217Val Uncertain significance ★ ⚠ same type
BLTP3A p.Ala1366Ser Uncertain significance ★ ⚠ same type
BLTP3A p.Ala257Thr Uncertain significance ★ ⚠ same type
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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/bltp3a-p-arg427trp (accessed [today's date]).

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