Is CHMP1A p.Arg68= (c.204C>T) pathogenic?

CHMP1A p.Arg68= (c.204C>T) is classified Conflicting classifications of pathogenicity in CHMP1A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-09). Rare (popmax 0.159%, sas); Associated with pontocerebellar hypoplasia type 8.

What condition is associated with CHMP1A p.Arg68= (c.204C>T)?

CHMP1A p.Arg68= (c.204C>T) is associated with pontocerebellar hypoplasia type 8 (ClinVar).

How common is CHMP1A p.Arg68= (c.204C>T) in the general population?

CHMP1A p.Arg68= (c.204C>T) is rare (popmax 0.159%, sas) (gnomAD).

CHMP1A p.Arg68=

c.204C>T · rs199628110 · VCV510863

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.159%, sas)

Conditions

pontocerebellar hypoplasia type 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.071	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3.4
Overall
CADD	0.051	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.159% South Asian · 145/91,086 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.13%

Overall 0.0244% 393/1,613,674 alleles · rare exomes 369/1,461,372 · genomes 24/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.159%	628
Middle Eastern	0.116%	866
Remaining individualsnot grpmax-eligible	0.0224%	4,463
European (non-Finnish)	0.0177%	5,645
Admixed American	0.015%	6,668
African / African-American	0.008%	12,507
East Asian	0.00446%	22,436
Finnishnot grpmax-eligible	0.00157%	63,726

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: CHMP1A
Protein: p.Arg68=
Coding: c.204C>T
MANE Select: NM_002768
dbSNP: rs199628110
Type: single nucleotide variant
Location: chr16:89649399 (GRCh38)
Gene constraint: LOEUF 1.045 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.44 · 4 PDB

Full CHMP1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia type 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHMP1A p.Arg68Cys Uncertain significance ★ ⚠ same residue
CHMP1A p.Arg68His Conflicting classifications of pathogenicity ★ ⚠ same residue
CHMP1A c.28-13G>A Pathogenic/Likely pathogenic ★★ same condition
CHMP1A p.Cys44Ser Uncertain significance ★★ ⚠ same condition
CHMP1A c.28-2A>G Likely pathogenic ★ same condition
CHMP1A c.106-3C>T Uncertain significance ★ same condition
CHMP1A c.*93G>A Uncertain significance ★ same condition
CHMP1A p.Ala22Val Conflicting classifications of pathogenicity ★ ⚠ same condition

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/chmp1a-p-arg68 (accessed [today's date]).

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