Is CHAMP1 p.Pro317= (c.951T>C) pathogenic?

CHAMP1 p.Pro317= (c.951T>C) is classified Benign in CHAMP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-08-23). Low-frequency (popmax 4.3%, eas); Associated with intellectual disability, autosomal dominant 40.

What condition is associated with CHAMP1 p.Pro317= (c.951T>C)?

CHAMP1 p.Pro317= (c.951T>C) is associated with intellectual disability, autosomal dominant 40 (ClinVar).

How common is CHAMP1 p.Pro317= (c.951T>C) in the general population?

CHAMP1 p.Pro317= (c.951T>C) is low-frequency (popmax 4.3%, eas) (gnomAD).

CHAMP1 p.Pro317=

c.951T>C · rs144765511 · VCV715527

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.3%, eas)

Conditions

intellectual disability, autosomal dominant 40

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 -0.2	GERP -0.69, phastCons 0.66
Overall
CADD	7.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.3% East Asian · 1,928/44,878 alleles

Filtering AF 4.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.07%

Overall 0.134% 2,156/1,614,022 alleles · low-frequency exomes 1,871/1,461,740 · genomes 285/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	4.3%	23
Remaining individualsnot grpmax-eligible	0.235%	425
South Asian	0.0439%	2,277
African / African-American	0.0227%	4,414
Middle Eastern	0.0165%	6,062
Admixed American	0.0117%	8,575
European (non-Finnish)	0.00136%	73,744

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: CHAMP1
Protein: p.Pro317=
Coding: c.951T>C
MANE Select: NM_032436
dbSNP: rs144765511
Type: single nucleotide variant
Location: chr13:114324793 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 48.04 · 4 PDB
Residue 317: the 'disordered' region; the 'mediates interaction with mad2l2' region

Full CHAMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal dominant 40 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHAMP1 p.Arg398Ter Pathogenic ★★ same condition
CHAMP1 p.Arg497Ter Pathogenic ★★ same condition
CHAMP1 p.Lys620Ter Pathogenic ★★ same condition
CHAMP1 p.Gly238Arg Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Pro477Ser Uncertain significance ★★ ⚠ same condition
CHAMP1 p.Pro309Leu Benign/Likely benign ★★ ⚠ same condition
CHAMP1 p.Gln115Ter Likely pathogenic ★ same condition
CHAMP1 p.Gln590Ter Pathogenic ★ 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/champ1-p-pro317 (accessed [today's date]).

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