Is CCDC185 p.Arg13Trp (c.37C>T) pathogenic?

CCDC185 p.Arg13Trp (c.37C>T) is classified Uncertain significance in CCDC185 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.1135); Very rare (popmax 0.00202%, amr).

How common is CCDC185 p.Arg13Trp (c.37C>T) in the general population?

CCDC185 p.Arg13Trp (c.37C>T) is very rare (popmax 0.00202%, amr) (gnomAD).

What do computational predictors say about CCDC185 p.Arg13Trp (c.37C>T)?

AlphaMissense predicts likely benign (score 0.1135) — an in-silico prediction, not a clinical call.

CCDC185 p.Arg13Trp

c.37C>T · VCV3486558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1135 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00202%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1135	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.02	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 -1.6	GERP -2.7
Regional constraint	o/e 1.19	unconstrained · MANE · 1,868 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	7.601	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 0.00202% Admixed American · 1/49,568 alleles

Filtering AF 0.000254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000163%

Overall 0.000585% 9/1,537,568 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00202%	49,568
South Asian	0.00123%	81,196
European (non-Finnish)	0.000611%	163,596

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: CCDC185
Protein: p.Arg13Trp
Coding: c.37C>T
MANE Select: NM_152610
Type: single nucleotide variant
Location: chr1:223393512 (GRCh38)
Gene constraint: LOEUF 1.695 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 69.31
Residue 13: the 'disordered' region

Full CCDC185 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC185 p.Arg13Pro Uncertain significance ★ ⚠ same residue
CCDC185 p.Ala364Val Uncertain significance ★ ⚠ same type
CCDC185 p.Ala404Thr Uncertain significance ★ ⚠ same type
CCDC185 p.Ala432Gly Uncertain significance ★ ⚠ same type
CCDC185 p.Ala441Ser Uncertain significance ★ ⚠ same type
CCDC185 p.Ala441Thr Uncertain significance ★ ⚠ same type
CCDC185 p.Ala510Val Uncertain significance ★ ⚠ same type
CCDC185 p.Ala55Val 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/ccdc185-p-arg13trp (accessed [today's date]).

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