Is CPM p.Val35Ile (c.103G>A) pathogenic?

CPM p.Val35Ile (c.103G>A) is classified Uncertain significance in CPM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: likely benign (0.0789); Absent from gnomAD v4.1.

How common is CPM p.Val35Ile (c.103G>A) in the general population?

CPM p.Val35Ile (c.103G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPM p.Val35Ile (c.103G>A)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

CPM p.Val35Ile

c.103G>A · VCV3269192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.52	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 0.18	GERP 0.63, phastCons 0.006
Regional constraint	o/e 0.80	unconstrained · MANE · 76 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	16.49	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: CPM
Protein: p.Val35Ile
Coding: c.103G>A
MANE Select: NM_198320
Type: single nucleotide variant
Location: chr12:68932735 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 1 PDB
Residue 35: an α-helix; the peptidase m14 domain

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

Similar variants

CPM p.Val35Ala Uncertain significance ★ ⚠ same residue
CPM p.Ala209Ser Uncertain significance ★ ⚠ same type
CPM p.Ala36Thr Uncertain significance ★ ⚠ same type
CPM p.Arg118Gln Uncertain significance ★ ⚠ same type
CPM p.Arg213Gln Uncertain significance ★ ⚠ same type
CPM p.Arg289Cys Uncertain significance ★ ⚠ same type
CPM p.Arg289Gly Uncertain significance ★ ⚠ same type
CPM p.Arg289His 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/cpm-p-val35ile (accessed [today's date]).

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