Is BPGM p.Arg140Trp (c.418C>T) pathogenic?

BPGM p.Arg140Trp (c.418C>T) is classified Uncertain significance in BPGM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.3065); Rare (popmax 0.132%, mid).

How common is BPGM p.Arg140Trp (c.418C>T) in the general population?

BPGM p.Arg140Trp (c.418C>T) is rare (popmax 0.132%, mid) (gnomAD).

What do computational predictors say about BPGM p.Arg140Trp (c.418C>T)?

AlphaMissense predicts likely benign (score 0.3065) — an in-silico prediction, not a clinical call.

BPGM p.Arg140Trp

c.418C>T · VCV4646411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3065 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3065	likely benign
REVEL	0.609	indeterminate
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 0.01 · regional, not allelic
Overall
CADD	28.6	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 0.132% Middle Eastern · 8/6,056 alleles

Filtering AF 0.0657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.048%

Overall 0.00223% 36/1,613,342 alleles · rare exomes 32/1,461,088 · genomes 4/152,254 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	757
African / African-American	0.012%	8,335
Admixed American	0.00667%	14,995
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asian	0.0011%	91,062
European (non-Finnish)	0.000933%	107,216

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.Arg140Trp
Coding: c.418C>T
MANE Select: NM_001724
Type: single nucleotide variant
Location: chr7:134661925 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 17 PDB
Residue 140: an α-helix

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

Similar variants

BPGM p.Arg140Gln Uncertain significance ★ ⚠ same residue
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

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-arg140trp (accessed [today's date]).

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