Is CCDC60 p.Pro188Leu (c.563C>T) pathogenic?

CCDC60 p.Pro188Leu (c.563C>T) is classified Uncertain significance in CCDC60 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: ambiguous (0.5137); Very rare (popmax 0.00134%, afr).

How common is CCDC60 p.Pro188Leu (c.563C>T) in the general population?

CCDC60 p.Pro188Leu (c.563C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CCDC60 p.Pro188Leu (c.563C>T)?

AlphaMissense predicts ambiguous (score 0.5137) — an in-silico prediction, not a clinical call.

CCDC60 p.Pro188Leu

c.563C>T · VCV3828695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5137 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5137	ambiguous
REVEL	0.214	benign-leaning
SaProt	LLR -4.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 206 kb · p 0.2 · regional, not allelic
Overall
CADD	26.6	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 0.00134% African / African-American · 1/74,700 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000683% 11/1,610,428 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,360
African / African-Americangrpmax	0.00134%	74,700
South Asian	0.0011%	90,894
European (non-Finnish)	0.00068%	147,158

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCDC60
Protein: p.Pro188Leu
Coding: c.563C>T
MANE Select: NM_178499
Type: single nucleotide variant
Location: chr12:119500083 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.25

Full CCDC60 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC60 p.Ser245Ile Uncertain significance ★★ ⚠ same type
CCDC60 p.Ala159Asp Uncertain significance ★ ⚠ same type
CCDC60 p.Ala159Thr Uncertain significance ★ ⚠ same type
CCDC60 p.Ala18Val Uncertain significance ★ ⚠ same type
CCDC60 p.Ala214Val Uncertain significance ★ ⚠ same type
CCDC60 p.Ala388Thr Uncertain significance ★ ⚠ same type
CCDC60 p.Ala451Glu Uncertain significance ★ ⚠ same type
CCDC60 p.Ala472Thr 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/ccdc60-p-pro188leu (accessed [today's date]).

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