Is CCDC185 p.Val413Met (c.1237G>A) pathogenic?

CCDC185 p.Val413Met (c.1237G>A) is classified Uncertain significance in CCDC185 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.0957); Rare (popmax 0.12%, nfe).

How common is CCDC185 p.Val413Met (c.1237G>A) in the general population?

CCDC185 p.Val413Met (c.1237G>A) is rare (popmax 0.12%, nfe) (gnomAD).

What do computational predictors say about CCDC185 p.Val413Met (c.1237G>A)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

CCDC185 p.Val413Met

c.1237G>A · rs146170796 · VCV2300561

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.12%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.51	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 -7.9	GERP -3.7
Regional constraint	o/e 1.19	unconstrained · MANE · 1,868 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	0.048	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 0.12% European (non-Finnish) · 1,409/1,178,992 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.0923% 1,487/1,611,372 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.12%	837
Remaining individualsnot grpmax-eligible	0.0657%	1,521
Admixed American	0.0402%	2,490
African / African-American	0.0147%	6,814
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,422
South Asian	0.0011%	90,716

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.Val413Met
Coding: c.1237G>A
MANE Select: NM_152610
dbSNP: rs146170796
Type: single nucleotide variant
Location: chr1:223394712 (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.Val413Leu 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-val413met (accessed [today's date]).

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