Is CCDC13 p.Arg425Trp (c.1273C>T) pathogenic?

CCDC13 p.Arg425Trp (c.1273C>T) is classified Uncertain significance in CCDC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely benign (0.1126); Very rare (popmax 0.00167%, amr).

How common is CCDC13 p.Arg425Trp (c.1273C>T) in the general population?

CCDC13 p.Arg425Trp (c.1273C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CCDC13 p.Arg425Trp (c.1273C>T)?

AlphaMissense predicts likely benign (score 0.1126) — an in-silico prediction, not a clinical call.

CCDC13 p.Arg425Trp

c.1273C>T · rs777005407 · VCV3138331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1126 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1126	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -10.91	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 1.6	GERP -2, phastCons 0.021
Regional constraint	o/e 0.94	unconstrained · MANE · 49 kb · p 0.094 · regional, not allelic
Overall
CADD	21.4	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 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
European (non-Finnish)	0.000339%	295,011

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.Arg425Trp
Coding: c.1273C>T
MANE Select: NM_144719
dbSNP: rs777005407
Type: single nucleotide variant
Location: chr3:42735805 (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

Similar variants

CCDC13 p.Arg425Gln Likely benign ★ ⚠ same residue
CCDC13 p.Glu565Lys Uncertain significance ★★ ⚠ same type
CCDC13 p.Ala129Thr Uncertain significance ★ ⚠ same type
CCDC13 p.Ala175Thr Uncertain significance ★ ⚠ same type
CCDC13 p.Ala187Thr Uncertain significance ★ ⚠ same type
CCDC13 p.Ala332Gly Uncertain significance ★ ⚠ same type
CCDC13 p.Ala3Val Uncertain significance ★ ⚠ same type
CCDC13 p.Ala517Val 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/ccdc13-p-arg425trp (accessed [today's date]).

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