Is CCDC13 p.Arg236Trp (c.706C>T) pathogenic?

CCDC13 p.Arg236Trp (c.706C>T) is classified Uncertain significance in CCDC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.1804); Very rare (popmax 0.00333%, amr).

How common is CCDC13 p.Arg236Trp (c.706C>T) in the general population?

CCDC13 p.Arg236Trp (c.706C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CCDC13 p.Arg236Trp (c.706C>T)?

AlphaMissense predicts likely benign (score 0.1804) — an in-silico prediction, not a clinical call.

CCDC13 p.Arg236Trp

c.706C>T · VCV3996407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1804	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -11.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.61, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 49 kb · p 0.094 · regional, not allelic
Overall
CADD	29.5	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 0.00333% Admixed American · 2/60,000 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000806% 13/1,613,742 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,000
African / African-American	0.00267%	37,450
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000678%	147,478

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: CCDC13
Protein: p.Arg236Trp
Coding: c.706C>T
MANE Select: NM_144719
Type: single nucleotide variant
Location: chr3:42747271 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.77

Full CCDC13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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CCDC13 p.Ala187Thr Uncertain significance ★ ⚠ same type
CCDC13 p.Ala332Gly Uncertain significance ★ ⚠ same type
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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/ccdc13-p-arg236trp (accessed [today's date]).

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