Is CCDC60 p.Ser460Phe (c.1379C>T) pathogenic?

CCDC60 p.Ser460Phe (c.1379C>T) is classified Uncertain significance in CCDC60 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-28). AlphaMissense: ambiguous (0.3679); Very rare (popmax 0.00668%, eas).

How common is CCDC60 p.Ser460Phe (c.1379C>T) in the general population?

CCDC60 p.Ser460Phe (c.1379C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CCDC60 p.Ser460Phe (c.1379C>T)?

AlphaMissense predicts ambiguous (score 0.3679) — an in-silico prediction, not a clinical call.

CCDC60 p.Ser460Phe

c.1379C>T · rs766116584 · VCV2622121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3679 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3679	ambiguous
REVEL	0.156	moderately benign-leaning
SaProt	LLR -9.65	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 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 206 kb · p 0.2 · regional, not allelic
Overall
CADD	28.6	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 0.00668% East Asian · 3/44,882 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00062% 10/1,613,646 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
Remaining individualsnot grpmax-eligible	0.0032%	31,232
South Asian	0.0011%	91,034
European (non-Finnish)	0.000339%	294,967

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.Ser460Phe
Coding: c.1379C>T
MANE Select: NM_178499
dbSNP: rs766116584
Type: single nucleotide variant
Location: chr12:119530891 (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-ser460phe (accessed [today's date]).

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