Is CCDC180 p.Pro58Arg (c.173C>G) pathogenic?

CCDC180 p.Pro58Arg (c.173C>G) is classified Uncertain significance in CCDC180 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-10). AlphaMissense: likely benign (0.0895); Ultra-rare (popmax 0.0331%, mid).

How common is CCDC180 p.Pro58Arg (c.173C>G) in the general population?

CCDC180 p.Pro58Arg (c.173C>G) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about CCDC180 p.Pro58Arg (c.173C>G)?

AlphaMissense predicts likely benign (score 0.0895) — an in-silico prediction, not a clinical call.

CCDC180 p.Pro58Arg

c.173C>G · VCV3486490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0895 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0895	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.33	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 -0.55	GERP -0.6
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0058 · regional, not allelic
Overall
CADD	11.2	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P102R vs ClinVar P58R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,046 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00475%

Overall 0.00561% 90/1,604,248 alleles · ultra-rare exomes 84/1,452,024 · genomes 6/152,224 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,023
Remaining individualsnot grpmax-eligible	0.00965%	10,361
Admixed American	0.00857%	11,664
European (non-Finnish)	0.00638%	15,677
African / African-American	0.00268%	37,252

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: CCDC180
Protein: p.Pro58Arg
Coding: c.173C>G
MANE Select: NM_020893
Type: single nucleotide variant
Location: chr9:97309517 (GRCh38)
Gene constraint: LOEUF 0.821 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.84

Full CCDC180 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC180 p.Ser812Cys Benign ★★ same type
CCDC180 c.-102C>G Uncertain significance ★ ⚠ same type
CCDC180 c.-104C>T Uncertain significance ★ ⚠ same type
CCDC180 c.-107C>G Uncertain significance ★ ⚠ same type
CCDC180 c.-129C>G Uncertain significance ★ ⚠ same type
CCDC180 p.Ala106Thr Uncertain significance ★ ⚠ same type
CCDC180 p.Ala1348Thr Uncertain significance ★ ⚠ same type
CCDC180 p.Ala149Val 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/ccdc180-p-pro58arg (accessed [today's date]).

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