Is CHMP5 p.Arg79Trp (c.235C>T) pathogenic?

CHMP5 p.Arg79Trp (c.235C>T) is classified Uncertain significance in CHMP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.9098); Very rare (popmax 0.00834%, amr).

How common is CHMP5 p.Arg79Trp (c.235C>T) in the general population?

CHMP5 p.Arg79Trp (c.235C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about CHMP5 p.Arg79Trp (c.235C>T)?

AlphaMissense predicts likely pathogenic (score 0.9098) — an in-silico prediction, not a clinical call.

CHMP5 p.Arg79Trp

c.235C>T · rs367617638 · VCV2374523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9098 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9098	likely pathogenic
REVEL	0.647	pathogenic-leaning
SaProt	LLR -17.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.27	acceptor loss, 13 bp away · masked 0 · deltas
Pangolin	Δ0.26	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 0.0049 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00834% Admixed American · 5/59,976 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00403% 65/1,613,550 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,995
East Asian	0.00668%	14,963
Remaining individualsnot grpmax-eligible	0.0064%	15,618
European (non-Finnish)	0.00424%	23,595
African / African-American	0.00401%	24,945

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: CHMP5
Protein: p.Arg79Trp
Coding: c.235C>T
MANE Select: NM_016410
dbSNP: rs367617638
Type: single nucleotide variant
Location: chr9:33270636 (GRCh38)
Gene constraint: LOEUF 1.441 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 6 PDB

Full CHMP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP5 p.Arg79Gln Uncertain significance ★ ⚠ same residue
CHMP5 p.Ala186Thr Uncertain significance ★ ⚠ same type
CHMP5 p.Ala191Val Uncertain significance ★ ⚠ same type
CHMP5 p.Asn143Ser Uncertain significance ★ ⚠ same type
CHMP5 p.Asn81Asp Uncertain significance ★ ⚠ same type
CHMP5 p.Asp159Glu Uncertain significance ★ ⚠ same type
CHMP5 p.Asp25Glu Uncertain significance ★ ⚠ same type
CHMP5 p.Asp39Ala 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/chmp5-p-arg79trp (accessed [today's date]).

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