Is CCDC60 p.Leu112fs (c.333del) pathogenic?

CCDC60 p.Leu112fs (c.333del) is classified Likely benign in CCDC60 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Rare (popmax 0.99%, mid).

How common is CCDC60 p.Leu112fs (c.333del) in the general population?

CCDC60 p.Leu112fs (c.333del) is rare (popmax 0.99%, mid) (gnomAD).

CCDC60 p.Leu112fs

c.333del · rs559574757 · VCV3025112

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.99%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.18	GERP -3.8
Overall
CADD	18.96	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.99% Middle Eastern · 60/6,062 alleles

Filtering AF 0.789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.717%

Overall 0.0615% 993/1,613,968 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.99%	101
Admixed American	0.135%	740
Remaining individualsnot grpmax-eligible	0.115%	868
South Asian	0.0736%	1,359
European (non-Finnish)	0.0592%	1,688
African / African-American	0.016%	6,251
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801

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.Leu112fs
Coding: c.333del
MANE Select: NM_178499
dbSNP: rs559574757
Type: Deletion
Location: chr12:119472155 (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

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-leu112fs (accessed [today's date]).

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