Is CCDC142 p.Ser366Asn (c.1097G>A) pathogenic?

CCDC142 p.Ser366Asn (c.1097G>A) is classified Likely benign in CCDC142 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0873); Rare (popmax 0.623%, sas).

How common is CCDC142 p.Ser366Asn (c.1097G>A) in the general population?

CCDC142 p.Ser366Asn (c.1097G>A) is rare (popmax 0.623%, sas) (gnomAD).

What do computational predictors say about CCDC142 p.Ser366Asn (c.1097G>A)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

CCDC142 p.Ser366Asn

c.1097G>A · VCV4649084

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.623%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -4.77	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 -0.22	GERP -3.1, phastCons 0.26
Regional constraint	o/e 1.03	unconstrained · MANE · 1,800 bp · p 0.41 · regional, not allelic
Overall
CADD	14.03	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 0.623% South Asian · 567/91,082 alleles

Filtering AF 0.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.563%

Overall 0.0379% 611/1,614,134 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.623%	161
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Middle Eastern	0.0495%	2,021
Admixed American	0.00333%	30,004
European (non-Finnish)	0.000593%	168,575

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.Ser366Asn
Coding: c.1097G>A
MANE Select: NM_001365575
Type: single nucleotide variant
Location: chr2:74481463 (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-ser366asn (accessed [today's date]).

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