Is CCDC142 p.Pro714Leu (c.2141C>T) pathogenic?

CCDC142 p.Pro714Leu (c.2141C>T) is classified Uncertain significance in CCDC142 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0877); Ultra-rare (popmax 0.0346%, afr).

How common is CCDC142 p.Pro714Leu (c.2141C>T) in the general population?

CCDC142 p.Pro714Leu (c.2141C>T) is ultra-rare (popmax 0.0346%, afr) (gnomAD).

What do computational predictors say about CCDC142 p.Pro714Leu (c.2141C>T)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

CCDC142 p.Pro714Leu

c.2141C>T · rs141112247 · VCV2377436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0346%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -5.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.3	GERP -0.56, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 1,126 bp · p 0.16 · regional, not allelic
Overall
CADD	22.1	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 0.0346% African / African-American · 26/75,058 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00235% 38/1,614,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0346%	2,887
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.008%	12,502
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.000424%	236,007

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.Pro714Leu
Coding: c.2141C>T
MANE Select: NM_001365575
dbSNP: rs141112247
Type: single nucleotide variant
Location: chr2:74474658 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.05
Residue 714: the 'disordered' region

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-pro714leu (accessed [today's date]).

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