Is CCDC142 p.Pro401Ser (c.1201C>T) pathogenic?

CCDC142 p.Pro401Ser (c.1201C>T) is classified Uncertain significance in CCDC142 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: likely benign (0.1515); Ultra-rare (popmax 0.06%, afr).

How common is CCDC142 p.Pro401Ser (c.1201C>T) in the general population?

CCDC142 p.Pro401Ser (c.1201C>T) is ultra-rare (popmax 0.06%, afr) (gnomAD).

What do computational predictors say about CCDC142 p.Pro401Ser (c.1201C>T)?

AlphaMissense predicts likely benign (score 0.1515) — an in-silico prediction, not a clinical call.

CCDC142 p.Pro401Ser

c.1201C>T · VCV3486055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1515 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1515	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,800 bp · p 0.41 · regional, not allelic
Overall
CADD	19.22	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.06% African / African-American · 45/75,034 alleles

Filtering AF 0.046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0411%

Overall 0.00372% 60/1,614,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.06%	1,667
Middle Eastern	0.0165%	6,062
Admixed American	0.01%	10,004
Remaining individualsnot grpmax-eligible	0.0064%	15,627
East Asian	0.00223%	44,888
European (non-Finnish)	0.000254%	393,338

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: CCDC142
Protein: p.Pro401Ser
Coding: c.1201C>T
MANE Select: NM_001365575
Type: single nucleotide variant
Location: chr2:74481280 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.05

Full CCDC142 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC142 p.Ala203Asp Uncertain significance ★ ⚠ same type
CCDC142 p.Ala226Val Uncertain significance ★ ⚠ same type
CCDC142 p.Ala227Thr Uncertain significance ★ ⚠ same type
CCDC142 p.Ala300Asp Uncertain significance ★ ⚠ same type
CCDC142 p.Ala331Gly Uncertain significance ★ ⚠ same type
CCDC142 p.Ala419Thr Uncertain significance ★ ⚠ same type
CCDC142 p.Ala603Gly Uncertain significance ★ ⚠ same type
CCDC142 p.Ala603Val 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/ccdc142-p-pro401ser (accessed [today's date]).

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