Is CCDC185 p.Pro341Arg (c.1022C>G) pathogenic?

CCDC185 p.Pro341Arg (c.1022C>G) is classified Uncertain significance in CCDC185 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.0829); Rare (popmax 0.1%, mid).

How common is CCDC185 p.Pro341Arg (c.1022C>G) in the general population?

CCDC185 p.Pro341Arg (c.1022C>G) is rare (popmax 0.1%, mid) (gnomAD).

What do computational predictors say about CCDC185 p.Pro341Arg (c.1022C>G)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

CCDC185 p.Pro341Arg

c.1022C>G · VCV3996849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.1%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -5.84	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 -1.4	GERP -2.6
Regional constraint	o/e 1.19	unconstrained · MANE · 1,868 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	3.608	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 0.1% Middle Eastern · 6/5,994 alleles

Filtering AF 0.0435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0297%

Overall 0.0024% 38/1,584,558 alleles · rare exomes 33/1,432,452 · genomes 5/152,106 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.1%	999
Ashkenazi Jewishnot grpmax-eligible	0.0514%	1,944
African / African-American	0.00943%	10,607
Remaining individualsnot grpmax-eligible	0.00489%	20,458
South Asian	0.00228%	43,838
European (non-Finnish)	0.000429%	233,319

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.Pro341Arg
Coding: c.1022C>G
MANE Select: NM_152610
Type: single nucleotide variant
Location: chr1:223394497 (GRCh38)
Gene constraint: LOEUF 1.695 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 69.31
Residue 341: the 'disordered' region

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-pro341arg (accessed [today's date]).

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