Is CHMP3 p.Ser47Ala (c.139T>G) pathogenic?

CHMP3 p.Ser47Ala (c.139T>G) is classified Uncertain significance in CHMP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.1173); Absent from gnomAD v4.1.

How common is CHMP3 p.Ser47Ala (c.139T>G) in the general population?

CHMP3 p.Ser47Ala (c.139T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHMP3 p.Ser47Ala (c.139T>G)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

CHMP3 p.Ser47Ala

c.139T>G · rs2466233565 · VCV3144443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.383	indeterminate
SaProt	LLR -9.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 22 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	24.0	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: CHMP3
Protein: p.Ser47Ala
Coding: c.139T>G
MANE Select: NM_016079
dbSNP: rs2466233565
Type: single nucleotide variant
Location: chr2:86529365 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 47: the 'intramolecular interaction with c-terminus' region; an α-helix

Full CHMP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP3 p.Ala52Val Uncertain significance ★ ⚠ same type
CHMP3 p.Arg39Thr Uncertain significance ★ ⚠ same type
CHMP3 p.Asp152Glu Uncertain significance ★ ⚠ same type
CHMP3 p.Asp153Asn Uncertain significance ★ ⚠ same type
CHMP3 p.Glu14Lys Uncertain significance ★ ⚠ same type
CHMP3 p.Glu18Lys Uncertain significance ★ ⚠ same type
CHMP3 p.Ile23Met Uncertain significance ★ ⚠ same type
CHMP3 p.Lys10Glu 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/chmp3-p-ser47ala (accessed [today's date]).

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