Is CCDC142 p.Ala72Thr (c.214G>A) pathogenic?

CCDC142 p.Ala72Thr (c.214G>A) is classified Uncertain significance in CCDC142 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely benign (0.095); Very rare (popmax 0.000255%, nfe).

How common is CCDC142 p.Ala72Thr (c.214G>A) in the general population?

CCDC142 p.Ala72Thr (c.214G>A) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CCDC142 p.Ala72Thr (c.214G>A)?

AlphaMissense predicts likely benign (score 0.095) — an in-silico prediction, not a clinical call.

CCDC142 p.Ala72Thr

c.214G>A · rs967443940 · VCV3138442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.095	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.32	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 4.5	GERP -2.7, phastCons 0.85
Regional constraint	o/e 1.03	unconstrained · MANE · 1,800 bp · p 0.41 · regional, not allelic
Overall
CADD	19.41	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 0.000255% European (non-Finnish) · 3/1,178,536 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,610,082 alleles · very rare

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.Ala72Thr
Coding: c.214G>A
MANE Select: NM_001365575
dbSNP: rs967443940
Type: single nucleotide variant
Location: chr2:74482624 (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.Ala72Val Uncertain significance ★ ⚠ same residue
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

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-ala72thr (accessed [today's date]).

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