Is CCDC142 p.Cys538Arg (c.1612T>C) pathogenic?

CCDC142 p.Cys538Arg (c.1612T>C) is classified Uncertain significance in CCDC142 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely benign (0.1372); Absent from gnomAD v4.1.

How common is CCDC142 p.Cys538Arg (c.1612T>C) in the general population?

CCDC142 p.Cys538Arg (c.1612T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC142 p.Cys538Arg (c.1612T>C)?

AlphaMissense predicts likely benign (score 0.1372) — an in-silico prediction, not a clinical call.

CCDC142 p.Cys538Arg

c.1612T>C · VCV3996513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1372 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1372	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -5.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 0.56, phastCons 0.96
Regional constraint	o/e 0.92	unconstrained · MANE · 1,126 bp · p 0.16 · regional, not allelic
Overall
CADD	16.06	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: CCDC142
Protein: p.Cys538Arg
Coding: c.1612T>C
MANE Select: NM_001365575
Type: single nucleotide variant
Location: chr2:74475618 (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-cys538arg (accessed [today's date]).

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