Is CCDC185 p.Trp313Arg (c.937T>C) pathogenic?

CCDC185 p.Trp313Arg (c.937T>C) is classified Uncertain significance in CCDC185 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely pathogenic (0.874); Very rare (popmax 0.00116%, sas).

How common is CCDC185 p.Trp313Arg (c.937T>C) in the general population?

CCDC185 p.Trp313Arg (c.937T>C) is very rare (popmax 0.00116%, sas) (gnomAD).

What do computational predictors say about CCDC185 p.Trp313Arg (c.937T>C)?

AlphaMissense predicts likely pathogenic (score 0.874) — an in-silico prediction, not a clinical call.

CCDC185 p.Trp313Arg

c.937T>C · rs1669618153 · VCV2620533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00116%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.874	likely pathogenic · top 1% in CCDC185
REVEL	0.17	moderately benign-leaning
SaProt	LLR -4.10	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 1,868 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	25.1	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 0.00116% South Asian · 1/86,032 alleles

Overall 0.000128% 2/1,567,958 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00116%	86,032
European (non-Finnish)	8.64e-05%	1,157,239

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.Trp313Arg
Coding: c.937T>C
MANE Select: NM_152610
dbSNP: rs1669618153
Type: single nucleotide variant
Location: chr1:223394412 (GRCh38)
Gene constraint: LOEUF 1.695 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 69.31

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

Similar variants

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
CCDC185 p.Ala564Thr 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-trp313arg (accessed [today's date]).

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