Is BLTP3A p.Ser974Phe (c.2921C>T) pathogenic?

BLTP3A p.Ser974Phe (c.2921C>T) is classified Uncertain significance in BLTP3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0922); Absent from gnomAD v4.1.

How common is BLTP3A p.Ser974Phe (c.2921C>T) in the general population?

BLTP3A p.Ser974Phe (c.2921C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BLTP3A p.Ser974Phe (c.2921C>T)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

BLTP3A p.Ser974Phe

c.2921C>T · VCV4214065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -8.70	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 2.1	GERP 2.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 80 kb · p 4.8e-07 · regional, not allelic
Overall
CADD	19.11	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BLTP3A
Protein: p.Ser974Phe
Coding: c.2921C>T
MANE Select: NM_017754
Type: single nucleotide variant
Location: chr6:34859277 (GRCh38)
Structure: AlphaFold pLDDT 67.37
Residue 974: the 'disordered' region

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-ser974phe (accessed [today's date]).

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