Is CHMP7 p.Val125Phe (c.373G>T) pathogenic?

CHMP7 p.Val125Phe (c.373G>T) is classified Uncertain significance in CHMP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.2728); Absent from gnomAD v4.1.

How common is CHMP7 p.Val125Phe (c.373G>T) in the general population?

CHMP7 p.Val125Phe (c.373G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHMP7 p.Val125Phe (c.373G>T)?

AlphaMissense predicts likely benign (score 0.2728) — an in-silico prediction, not a clinical call.

CHMP7 p.Val125Phe

c.373G>T · rs2486437652 · VCV2556304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2728 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2728	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -7.60	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.075 · regional, not allelic
Overall
CADD	24.8	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: CHMP7
Protein: p.Val125Phe
Coding: c.373G>T
MANE Select: NM_152272
dbSNP: rs2486437652
Type: single nucleotide variant
Location: chr8:23249283 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.53

Full CHMP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP7 p.Ala297= Benign ★★ same type
CHMP7 p.Leu347= Benign ★★ same type
CHMP7 p.Ala112Asp Uncertain significance ★ ⚠ same type
CHMP7 p.Ala12Gly Uncertain significance ★ ⚠ same type
CHMP7 p.Ala146Thr Uncertain significance ★ ⚠ same type
CHMP7 p.Ala160Gly Uncertain significance ★ ⚠ same type
CHMP7 p.Ala17Thr Uncertain significance ★ ⚠ same type
CHMP7 p.Ala188Val 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/chmp7-p-val125phe (accessed [today's date]).

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