Is BLTP2 p.Ser2229Phe (c.6686C>T) pathogenic?

BLTP2 p.Ser2229Phe (c.6686C>T) is classified Uncertain significance in BLTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.4053); Very rare (popmax 0.00769%, sas).

How common is BLTP2 p.Ser2229Phe (c.6686C>T) in the general population?

BLTP2 p.Ser2229Phe (c.6686C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about BLTP2 p.Ser2229Phe (c.6686C>T)?

AlphaMissense predicts ambiguous (score 0.4053) — an in-silico prediction, not a clinical call.

BLTP2 p.Ser2229Phe

c.6686C>T · VCV4213761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4053	ambiguous
REVEL	0.289	benign-leaning
SaProt	LLR -7.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 9,298 bp · p 1.1e-21 · regional, not allelic
Overall
CADD	26.3	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 0.00769% South Asian · 7/90,986 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00062% 10/1,613,570 alleles · very rare exomes 8/1,461,396 · genomes 2/152,174 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	12,998
African / African-American	0.00401%	24,963

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: BLTP2
Protein: p.Ser2229Phe
Coding: c.6686C>T
MANE Select: NM_014680
Type: single nucleotide variant
Location: chr17:28615086 (GRCh38)
Structure: AlphaFold pLDDT 71.37

Full BLTP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP2 p.Ala1395Ser Uncertain significance ★ ⚠ same type
BLTP2 p.Ala1564Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala1826Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala248Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala324Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala393Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala539Thr Uncertain significance ★ ⚠ same type
BLTP2 p.Ala694Gly 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/bltp2-p-ser2229phe (accessed [today's date]).

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