Is CCDC42 p.Arg136Gln (c.407G>A) pathogenic?

CCDC42 p.Arg136Gln (c.407G>A) is classified Uncertain significance in CCDC42 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: likely benign (0.0746); Very rare (popmax 0.00534%, afr).

How common is CCDC42 p.Arg136Gln (c.407G>A) in the general population?

CCDC42 p.Arg136Gln (c.407G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CCDC42 p.Arg136Gln (c.407G>A)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

CCDC42 p.Arg136Gln

c.407G>A · VCV3997025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -5.19	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 0.78	GERP -1.5, phastCons 0.007
Regional constraint	o/e 0.91	unconstrained · MANE · 14 kb · p 0.066 · regional, not allelic
Overall
CADD	19.19	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 0.00534% African / African-American · 4/74,930 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,732
Admixed American	0.005%	20,006
East Asian	0.00446%	22,439
European (non-Finnish)	0.00127%	78,669
South Asian	0.0011%	91,088

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: CCDC42
Protein: p.Arg136Gln
Coding: c.407G>A
MANE Select: NM_144681
Type: single nucleotide variant
Location: chr17:8741559 (GRCh38)
Gene constraint: LOEUF 1.222 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.54

Full CCDC42 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC42 p.Ala107Thr Uncertain significance ★ ⚠ same type
CCDC42 p.Ala111Asp Uncertain significance ★ ⚠ same type
CCDC42 p.Ala134Thr Uncertain significance ★ ⚠ same type
CCDC42 p.Ala199Ser Uncertain significance ★ ⚠ same type
CCDC42 p.Ala262Thr Uncertain significance ★ ⚠ same type
CCDC42 p.Arg104Gln Uncertain significance ★ ⚠ same type
CCDC42 p.Arg16Pro Uncertain significance ★ ⚠ same type
CCDC42 p.Arg198His 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/ccdc42-p-arg136gln (accessed [today's date]).

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