Is CCDC120 p.Pro554Ser (c.1660C>T) pathogenic?

CCDC120 p.Pro554Ser (c.1660C>T) is classified Uncertain significance in CCDC120 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0772); Very rare (popmax 0.00222%, amr).

How common is CCDC120 p.Pro554Ser (c.1660C>T) in the general population?

CCDC120 p.Pro554Ser (c.1660C>T) is very rare (popmax 0.00222%, amr) (gnomAD).

What do computational predictors say about CCDC120 p.Pro554Ser (c.1660C>T)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

CCDC120 p.Pro554Ser

c.1660C>T · VCV4835685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.54	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 0.3	GERP 0.14, phastCons 0.98
Regional constraint	o/e 1.02	unconstrained · MANE · 4,747 bp · p 0.65 · regional, not allelic
Overall
CADD	4.892	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P519S vs ClinVar P554S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00222% Admixed American · 1/45,059 alleles

Overall 9.25e-05% 1/1,081,483 alleles · very rare

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: CCDC120
Protein: p.Pro554Ser
Coding: c.1660C>T
MANE Select: NM_001163321
Type: single nucleotide variant
Location: chrX:49067774 (GRCh38)
Structure: AlphaFold pLDDT 56.34

Full CCDC120 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC120 c.63+12A>G Uncertain significance ★ same type
CCDC120 p.Ala126Thr Uncertain significance ★ ⚠ same type
CCDC120 p.Ala161Thr Uncertain significance ★ ⚠ same type
CCDC120 p.Ala164Gly Uncertain significance ★ ⚠ same type
CCDC120 p.Ala348Thr Uncertain significance ★ ⚠ same type
CCDC120 p.Ala376Val Uncertain significance ★ ⚠ same type
CCDC120 p.Ala405Thr Uncertain significance ★ ⚠ same type
CCDC120 p.Ala441Pro 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/ccdc120-p-pro554ser (accessed [today's date]).

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