Is BCHE p.Ser515Thr (c.1544G>C) pathogenic?

BCHE p.Ser515Thr (c.1544G>C) is classified Uncertain significance in BCHE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-10). AlphaMissense: likely benign (0.0717); Ultra-rare (popmax 0.0174%, afr); Associated with Inborn genetic diseases.

What condition is associated with BCHE p.Ser515Thr (c.1544G>C)?

BCHE p.Ser515Thr (c.1544G>C) is associated with Inborn genetic diseases (ClinVar).

How common is BCHE p.Ser515Thr (c.1544G>C) in the general population?

BCHE p.Ser515Thr (c.1544G>C) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about BCHE p.Ser515Thr (c.1544G>C)?

AlphaMissense predicts likely benign (score 0.0717) — an in-silico prediction, not a clinical call.

BCHE p.Ser515Thr

c.1544G>C · rs371869257 · VCV1343601

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0717 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0717	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.24	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 0.36	GERP 0.053, phastCons 0.11
Regional constraint	o/e 1.20	unconstrained · MANE · 58 kb · p 1.8e-07 · regional, not allelic
Overall
CADD	14.19	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

Grpmax group 0.0174% African / African-American · 13/74,814 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00814%

Overall 0.000807% 13/1,611,442 alleles · ultra-rare

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: BCHE
Protein: p.Ser515Thr
Coding: c.1544G>C
MANE Select: NM_000055
dbSNP: rs371869257
Type: single nucleotide variant
Location: chr3:165786285 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.30 · 111 PDB
Residue 515: an α-helix; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCHE p.Ile538Thr Uncertain significance ★★ ⚠ same condition
BCHE p.Met109Ile Uncertain significance ★★ ⚠ same condition
BCHE p.Ala430Asp Uncertain significance ★ ⚠ same condition
BCHE p.Ala444Thr Uncertain significance ★ ⚠ same condition
BCHE p.Ala544Pro Uncertain significance ★ ⚠ same condition
BCHE p.Ala544Val Uncertain significance ★ ⚠ same condition
BCHE p.Ala567Val Uncertain significance ★ ⚠ same condition
BCHE p.Arg481Lys Uncertain significance ★ ⚠ same condition

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/bche-p-ser515thr (accessed [today's date]).

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