Is BPGM p.Leu165Phe (c.493C>T) pathogenic?

BPGM p.Leu165Phe (c.493C>T) is classified Uncertain significance in BPGM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: ambiguous (0.5348); Very rare (popmax 0.00373%, nfe).

How common is BPGM p.Leu165Phe (c.493C>T) in the general population?

BPGM p.Leu165Phe (c.493C>T) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about BPGM p.Leu165Phe (c.493C>T)?

AlphaMissense predicts ambiguous (score 0.5348) — an in-silico prediction, not a clinical call.

BPGM p.Leu165Phe

c.493C>T · rs755896639 · VCV2215065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5348	ambiguous
REVEL	0.496	indeterminate
SaProt	LLR -5.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 0.01 · regional, not allelic
Overall
CADD	23.9	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 0.00373% European (non-Finnish) · 44/1,180,030 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00273% 44/1,614,036 alleles · very rare exomes 39/1,461,862 · genomes 5/152,174 · joint denominator

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: BPGM
Protein: p.Leu165Phe
Coding: c.493C>T
MANE Select: NM_001724
dbSNP: rs755896639
Type: single nucleotide variant
Location: chr7:134662000 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 17 PDB
Residue 165: an α-helix

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

Similar variants

BPGM p.Glu176Lys Uncertain significance ★★ ⚠ same type
BPGM p.His11Asn Uncertain significance ★★ ⚠ same type
BPGM p.His198Gln Uncertain significance ★★ ⚠ same type
BPGM p.Arg62= Likely benign ★★ same type
BPGM p.Leu162= Likely benign ★★ same type
BPGM p.Arg90Cys Pathogenic ★ same type
BPGM p.Ala243Val Uncertain significance ★ ⚠ same type
BPGM p.Ala244Val 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/bpgm-p-leu165phe (accessed [today's date]).

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