Is CHMP6 p.Gly55Ser (c.163G>A) pathogenic?

CHMP6 p.Gly55Ser (c.163G>A) is classified Benign in CHMP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.2462); Low-frequency (popmax 3.11%, afr).

How common is CHMP6 p.Gly55Ser (c.163G>A) in the general population?

CHMP6 p.Gly55Ser (c.163G>A) is low-frequency (popmax 3.11%, afr) (gnomAD).

What do computational predictors say about CHMP6 p.Gly55Ser (c.163G>A)?

AlphaMissense predicts likely benign (score 0.2462) — an in-silico prediction, not a clinical call.

CHMP6 p.Gly55Ser

c.163G>A · rs61037507 · VCV777275

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2462 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.11%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2462	likely benign
REVEL	0.479	indeterminate
SaProt	LLR -9.90	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 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,231 bp · p 0.75 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.11% African / African-American · 2,253/72,442 alleles

Filtering AF 3% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.96%

Overall 0.166% 2,614/1,571,004 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.11%	32
Admixed American	0.274%	364
Remaining individualsnot grpmax-eligible	0.214%	468
Middle Eastern	0.185%	542
South Asian	0.00702%	14,251
European (non-Finnish)	0.00594%	16,829

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: CHMP6
Protein: p.Gly55Ser
Coding: c.163G>A
MANE Select: NM_024591
dbSNP: rs61037507
Type: single nucleotide variant
Location: chr17:80994680 (GRCh38)
Gene constraint: LOEUF 0.599 · pLI 0.76 (gnomAD)
Structure: AlphaFold pLDDT 82.51 · 2 PDB
Residue 55: a UniProt-annotated variant site (in)

Full CHMP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHMP6 p.Asn185= Benign ★★ same type
CHMP6 p.Ala190Asp Uncertain significance ★ ⚠ same type
CHMP6 p.Ala46Thr Uncertain significance ★ ⚠ same type
CHMP6 p.Arg12Pro Uncertain significance ★ ⚠ same type
CHMP6 p.Arg138Gln Uncertain significance ★ ⚠ same type
CHMP6 p.Arg45Cys Uncertain significance ★ ⚠ same type
CHMP6 p.Arg45His Uncertain significance ★ ⚠ same type
CHMP6 p.Arg49Gln 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/chmp6-p-gly55ser (accessed [today's date]).

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