Is CCDC60 p.Ala214Val (c.641C>T) pathogenic?

CCDC60 p.Ala214Val (c.641C>T) is classified Uncertain significance in CCDC60 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely benign (0.084); Ultra-rare (popmax 0.0166%, mid).

How common is CCDC60 p.Ala214Val (c.641C>T) in the general population?

CCDC60 p.Ala214Val (c.641C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about CCDC60 p.Ala214Val (c.641C>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

CCDC60 p.Ala214Val

c.641C>T · VCV4221350

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP -0.34, phastCons 0.004
Regional constraint	o/e 0.95	unconstrained · MANE · 206 kb · p 0.2 · regional, not allelic
Overall
CADD	18.81	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

Grpmax group 0.0166% Middle Eastern · 1/6,032 alleles

Filtering AF 0.00668% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00487%

Overall 0.00131% 21/1,607,448 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,032
Admixed American	0.0135%	7,418
African / African-American	0.00403%	24,805
East Asian	0.00224%	44,594
Remaining individualsnot grpmax-eligible	0.00161%	62,206
European (non-Finnish)	0.000595%	167,988

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.Ala214Val
Coding: c.641C>T
MANE Select: NM_178499
Type: single nucleotide variant
Location: chr12:119500161 (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.Ala388Thr Uncertain significance ★ ⚠ same type
CCDC60 p.Ala451Glu Uncertain significance ★ ⚠ same type
CCDC60 p.Ala472Thr Uncertain significance ★ ⚠ same type
CCDC60 p.Ala548Thr 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-ala214val (accessed [today's date]).

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