Is CPAP p.Ile1207Met (c.3621C>G) pathogenic?

CPAP p.Ile1207Met (c.3621C>G) is classified Uncertain significance in CPAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-07-02). AlphaMissense: likely benign (0.1616); Ultra-rare (popmax 0.0681%, afr).

How common is CPAP p.Ile1207Met (c.3621C>G) in the general population?

CPAP p.Ile1207Met (c.3621C>G) is ultra-rare (popmax 0.0681%, afr) (gnomAD).

What do computational predictors say about CPAP p.Ile1207Met (c.3621C>G)?

AlphaMissense predicts likely benign (score 0.1616) — an in-silico prediction, not a clinical call.

CPAP p.Ile1207Met

c.3621C>G · rs145882096 · VCV420308

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1616 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1616	likely benign
REVEL	0.554	indeterminate
SaProt	LLR -9.45	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 2.9	GERP 0.012, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 30 kb · p 0.11 · regional, not allelic
Overall
CADD	23.3	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 0.0681% African / African-American · 51/74,910 alleles

Filtering AF 0.0532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0479%

Overall 0.00409% 66/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0681%	1,469
Middle Eastern	0.0164%	6,084
Admixed American	0.0117%	8,571
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Finnishnot grpmax-eligible	0.00156%	64,036

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: CPAP
Protein: p.Ile1207Met
Coding: c.3621C>G
MANE Select: NM_018451
dbSNP: rs145882096
Type: single nucleotide variant
Location: chr13:24884243 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 1207: the 'interaction with stil' region

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

Similar variants

CPAP p.Ile1207Asn Uncertain significance ★★ ⚠ same residue
CPAP c.2693-2A>G Likely pathogenic ★★ same type
CPAP p.Arg1298Gln Likely pathogenic ★★ same type
CPAP p.Arg378Ter Pathogenic ★★ same type
CPAP p.Arg566Ter Pathogenic/Likely pathogenic ★★ same type
CPAP p.Arg902Ter Pathogenic/Likely pathogenic ★★ same type
CPAP p.Arg958Ter Pathogenic/Likely pathogenic ★★ same type
CPAP p.Gln14Ter Pathogenic/Likely pathogenic ★★ 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/cpap-p-ile1207met (accessed [today's date]).

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