Is CCDC60 p.Lys404Arg (c.1211A>G) pathogenic?

CCDC60 p.Lys404Arg (c.1211A>G) is classified Uncertain significance in CCDC60 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1052); Absent from gnomAD v4.1.

How common is CCDC60 p.Lys404Arg (c.1211A>G) in the general population?

CCDC60 p.Lys404Arg (c.1211A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC60 p.Lys404Arg (c.1211A>G)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

CCDC60 p.Lys404Arg

c.1211A>G · VCV4221365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.02	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 4.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 206 kb · p 0.2 · regional, not allelic
Overall
CADD	19.41	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC60
Protein: p.Lys404Arg
Coding: c.1211A>G
MANE Select: NM_178499
Type: single nucleotide variant
Location: chr12:119523800 (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-lys404arg (accessed [today's date]).

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