Is BLTP3A p.Ser1337Pro (c.4009T>C) pathogenic?

BLTP3A p.Ser1337Pro (c.4009T>C) is classified Uncertain significance in BLTP3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: ambiguous (0.4886); Very rare (popmax 0.0011%, sas).

How common is BLTP3A p.Ser1337Pro (c.4009T>C) in the general population?

BLTP3A p.Ser1337Pro (c.4009T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BLTP3A p.Ser1337Pro (c.4009T>C)?

AlphaMissense predicts ambiguous (score 0.4886) — an in-silico prediction, not a clinical call.

BLTP3A p.Ser1337Pro

c.4009T>C · VCV3991838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4886	ambiguous
REVEL	0.128	moderately benign-leaning
SaProt	LLR -9.21	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.52 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 0.99, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 80 kb · p 4.8e-07 · regional, not allelic
Overall
CADD	24.7	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 0.0011% South Asian · 1/91,044 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,534 alleles · very rare exomes 4/1,461,302 · genomes 0/152,232 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,044
European (non-Finnish)	0.000254%	393,331

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.Ser1337Pro
Coding: c.4009T>C
MANE Select: NM_017754
Type: single nucleotide variant
Location: chr6:34871611 (GRCh38)
Structure: AlphaFold pLDDT 67.37

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

Similar variants

BLTP3A p.Val1190Phe Uncertain significance ★★ ⚠ same type
BLTP3A p.Ala1021Gly Uncertain significance ★ ⚠ same type
BLTP3A p.Ala1174Pro Uncertain significance ★ ⚠ same type
BLTP3A p.Ala1217Val Uncertain significance ★ ⚠ same type
BLTP3A p.Ala1366Ser Uncertain significance ★ ⚠ same type
BLTP3A p.Ala257Thr Uncertain significance ★ ⚠ same type
BLTP3A p.Ala263Ser Uncertain significance ★ ⚠ same type
BLTP3A p.Ala373Ser 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/bltp3a-p-ser1337pro (accessed [today's date]).

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