Is BLTP1 p.Ser4118= (c.12354G>A) pathogenic?

BLTP1 p.Ser4118= (c.12354G>A) is classified Likely benign in BLTP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-25). Rare (popmax 0.24%, nfe).

How common is BLTP1 p.Ser4118= (c.12354G>A) in the general population?

BLTP1 p.Ser4118= (c.12354G>A) is rare (popmax 0.24%, nfe) (gnomAD).

BLTP1 p.Ser4118=

c.12354G>A · rs201672584 · VCV2655068

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.24%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.045	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.2
Overall
CADD	3.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.24% European (non-Finnish) · 2,834/1,178,928 alleles

Filtering AF 0.233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.23%

Overall 0.215% 3,473/1,611,842 alleles · rare exomes 3,184/1,459,658 · genomes 289/152,184 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.604%	166
European (non-Finnish)grpmax	0.24%	416
Remaining individualsnot grpmax-eligible	0.17%	589
African / African-American	0.146%	687
Middle Eastern	0.0828%	1,208
Admixed American	0.0485%	2,060
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,552
South Asian	0.00331%	30,245

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: BLTP1
Protein: p.Ser4118=
Coding: c.12354G>A
MANE Select: NM_001384125
dbSNP: rs201672584
Type: single nucleotide variant
Location: chr4:122336960 (GRCh38)
Residue 4118: the 'disordered' region; a UniProt-annotated variant site (in alkkucs)

Full BLTP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP1 p.Arg968Cys Likely pathogenic ★★ ⚠ same type
BLTP1 c.1498+4A>G Uncertain significance ★★ same type
BLTP1 p.Ala2332Thr Uncertain significance ★★ ⚠ same type
BLTP1 p.Arg1317His Uncertain significance ★★ same type
BLTP1 p.Arg1791Lys Uncertain significance ★★ ⚠ same type
BLTP1 p.Arg2095His Uncertain significance ★★ same type
BLTP1 p.Arg2279Cys Uncertain significance ★★ same type
BLTP1 p.Arg3665Gln 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/bltp1-p-ser4118 (accessed [today's date]).

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