Is CPAP p.Asn321Lys (c.963T>A) pathogenic?

CPAP p.Asn321Lys (c.963T>A) is classified Uncertain significance in CPAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). AlphaMissense: likely benign (0.2768); Absent from gnomAD v4.1.

How common is CPAP p.Asn321Lys (c.963T>A) in the general population?

CPAP p.Asn321Lys (c.963T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPAP p.Asn321Lys (c.963T>A)?

AlphaMissense predicts likely benign (score 0.2768) — an in-silico prediction, not a clinical call.

CPAP p.Asn321Lys

c.963T>A · rs2541703882 · VCV2771805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2768 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2768	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.5, 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPAP
Protein: p.Asn321Lys
Coding: c.963T>A
MANE Select: NM_018451
dbSNP: rs2541703882
Type: single nucleotide variant
Location: chr13:24908029 (GRCh38)
Structure: AlphaFold pLDDT 56.70 · 6 PDB
Residue 321: the 'alpha/beta-tubulin binding' region

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

Similar variants

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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
CPAP p.Gln657Ter 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-asn321lys (accessed [today's date]).

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