Is CPD p.Leu76Arg (c.227T>G) pathogenic?

CPD p.Leu76Arg (c.227T>G) is classified Uncertain significance in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely benign (0.0811); Absent from gnomAD v4.1.

How common is CPD p.Leu76Arg (c.227T>G) in the general population?

CPD p.Leu76Arg (c.227T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPD p.Leu76Arg (c.227T>G)?

AlphaMissense predicts likely benign (score 0.0811) — an in-silico prediction, not a clinical call.

CPD p.Leu76Arg

c.227T>G · rs1041634728 · VCV2405684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0811 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0811	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.72	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 3.1	GERP -0.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 42 kb · p 0.76 · regional, not allelic
Overall
CADD	18.06	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPD
Protein: p.Leu76Arg
Coding: c.227T>G
MANE Select: NM_001304
dbSNP: rs1041634728
Type: single nucleotide variant
Location: chr17:30379207 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.14 · 3 PDB
Residue 76: the peptidase m14 1 domain

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

Similar variants

CPD p.Arg5= Benign ★★ same type
CPD p.Lys499Arg Benign ★★ same type
CPD p.Val677= Benign ★★ same type
CPD p.Ala122Val Uncertain significance ★ ⚠ same type
CPD p.Ala1263Thr Uncertain significance ★ ⚠ same type
CPD p.Ala157Val Uncertain significance ★ ⚠ same type
CPD p.Ala158Val Uncertain significance ★ ⚠ same type
CPD p.Ala46Val 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/cpd-p-leu76arg (accessed [today's date]).

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