Is CHAMP1 p.Ile36Phe (c.106A>T) pathogenic?

CHAMP1 p.Ile36Phe (c.106A>T) is classified Uncertain significance in CHAMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-05-19). AlphaMissense: likely benign (0.2533); Ultra-rare (popmax 0.0493%, mid).

How common is CHAMP1 p.Ile36Phe (c.106A>T) in the general population?

CHAMP1 p.Ile36Phe (c.106A>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about CHAMP1 p.Ile36Phe (c.106A>T)?

AlphaMissense predicts likely benign (score 0.2533) — an in-silico prediction, not a clinical call.

CHAMP1 p.Ile36Phe

c.106A>T · rs781988354 · VCV434756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2533 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2533	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP -3.4, phastCons 0.91
Regional constraint	o/e 0.70	unconstrained · MANE · 292 bp · p 0.00085 · regional, not allelic
Overall
CADD	18.65	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

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.000681% 11/1,614,098 alleles · ultra-rare exomes 10/1,461,884 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.000424%	236,009

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.Ile36Phe
Coding: c.106A>T
MANE Select: NM_032436
dbSNP: rs781988354
Type: single nucleotide variant
Location: chr13:114323948 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 48.04 · 4 PDB

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

Similar variants

CHAMP1 p.Ile36Met Uncertain significance ★ ⚠ same residue
CHAMP1 p.Arg398Ter Pathogenic ★★ same type
CHAMP1 p.Arg497Ter Pathogenic ★★ same type
CHAMP1 p.Lys620Ter Pathogenic ★★ same type
CHAMP1 p.Tyr709Ter Pathogenic/Likely pathogenic ★★ same type
CHAMP1 p.Ala304Val Uncertain significance ★★ ⚠ same type
CHAMP1 p.Glu195Gly Uncertain significance ★★ ⚠ same type
CHAMP1 p.Glu524Gly 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/champ1-p-ile36phe (accessed [today's date]).

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