Is CHMP1B p.Val180= (c.540G>T) pathogenic?

CHMP1B p.Val180= (c.540G>T) is classified Likely benign in CHMP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-01). Rare (popmax 0.112%, afr).

How common is CHMP1B p.Val180= (c.540G>T) in the general population?

CHMP1B p.Val180= (c.540G>T) is rare (popmax 0.112%, afr) (gnomAD).

CHMP1B p.Val180=

c.540G>T · rs141531709 · VCV1013393

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.112%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 1.9, phastCons 1
Overall
CADD	7.426	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.112% African / African-American · 84/75,046 alleles

Filtering AF 0.0926% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0855%

Overall 0.00985% 159/1,613,592 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.112%	893
Middle Eastern	0.0331%	3,025
Remaining individualsnot grpmax-eligible	0.0272%	3,674
Admixed American	0.02%	4,996
European (non-Finnish)	0.00373%	26,814

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: CHMP1B
Protein: p.Val180=
Coding: c.540G>T
MANE Select: NM_020412
dbSNP: rs141531709
Type: single nucleotide variant
Location: chr18:11852051 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 81.29 · 11 PDB
Residue 180: the 'disordered' region; the 'interaction with spast' region; the 'interaction with vta1' region; the 'interaction with vps4a, mitd1 and stambp' region

Full CHMP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP1B p.Ala31Pro Uncertain significance ★ ⚠ same type
CHMP1B p.Ala48Gly Uncertain significance ★ ⚠ same type
CHMP1B p.Ala62Glu Uncertain significance ★ ⚠ same type
CHMP1B p.Arg191Ile Uncertain significance ★ ⚠ same type
CHMP1B p.Arg49Lys Uncertain significance ★ ⚠ same type
CHMP1B p.Arg57Pro Uncertain significance ★ ⚠ same type
CHMP1B p.Arg78Gly Uncertain significance ★ ⚠ same type
CHMP1B p.Asn44Ser 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/chmp1b-p-val180 (accessed [today's date]).

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