Is CHMP5 p.Asn81Asp (c.241A>G) pathogenic?

CHMP5 p.Asn81Asp (c.241A>G) is classified Uncertain significance in CHMP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely pathogenic (0.6981); Very rare (popmax 0.000593%, nfe).

How common is CHMP5 p.Asn81Asp (c.241A>G) in the general population?

CHMP5 p.Asn81Asp (c.241A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CHMP5 p.Asn81Asp (c.241A>G)?

AlphaMissense predicts likely pathogenic (score 0.6981) — an in-silico prediction, not a clinical call.

CHMP5 p.Asn81Asp

c.241A>G · VCV4002455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6981	likely pathogenic
REVEL	0.319	indeterminate
SaProt	LLR -11.68	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 16 kb · p 0.0049 · regional, not allelic
Overall
CADD	25.3	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 0.000593% European (non-Finnish) · 7/1,180,008 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,614,032 alleles · very rare

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.Asn81Asp
Coding: c.241A>G
MANE Select: NM_016410
Type: single nucleotide variant
Location: chr9:33270642 (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.Ala186Thr Uncertain significance ★ ⚠ same type
CHMP5 p.Ala191Val Uncertain significance ★ ⚠ same type
CHMP5 p.Arg79Gln Uncertain significance ★ ⚠ same type
CHMP5 p.Arg79Trp Uncertain significance ★ ⚠ same type
CHMP5 p.Asn143Ser 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-asn81asp (accessed [today's date]).

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