Is BLTP3B p.Ala231Thr (c.691G>A) pathogenic?

BLTP3B p.Ala231Thr (c.691G>A) is classified Uncertain significance in BLTP3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: ambiguous (0.3463); Ultra-rare (popmax 0.0134%, sas).

How common is BLTP3B p.Ala231Thr (c.691G>A) in the general population?

BLTP3B p.Ala231Thr (c.691G>A) is ultra-rare (popmax 0.0134%, sas) (gnomAD).

What do computational predictors say about BLTP3B p.Ala231Thr (c.691G>A)?

AlphaMissense predicts ambiguous (score 0.3463) — an in-silico prediction, not a clinical call.

BLTP3B p.Ala231Thr

c.691G>A · VCV3824608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3463 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3463	ambiguous
REVEL	0.254	benign-leaning
SaProt	LLR -11.44	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 54 kb · p 5.9e-07 · regional, not allelic
Overall
CADD	24.9	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 0.0134% South Asian · 12/89,476 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00603%

Overall 0.000961% 14/1,456,592 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0134%	7,456
Remaining individualsnot grpmax-eligible	0.00321%	31,158

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: BLTP3B
Protein: p.Ala231Thr
Coding: c.691G>A
MANE Select: NM_015054
Type: single nucleotide variant
Location: chr12:100095816 (GRCh38)
Structure: AlphaFold pLDDT 67.53

Full BLTP3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP3B p.Ala231Ser Uncertain significance ★ ⚠ same residue
BLTP3B p.Leu491= Benign ★★ same type
BLTP3B p.Ala109Val Uncertain significance ★ ⚠ same type
BLTP3B p.Ala1162Thr Uncertain significance ★ ⚠ same type
BLTP3B p.Ala1272Ser Uncertain significance ★ ⚠ same type
BLTP3B p.Ala257Gly Uncertain significance ★ ⚠ same type
BLTP3B p.Ala66Thr Uncertain significance ★ ⚠ same type
BLTP3B p.Ala847Val 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/bltp3b-p-ala231thr (accessed [today's date]).

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