Is CCDC125 p.Ser290Pro (c.868T>C) pathogenic?

CCDC125 p.Ser290Pro (c.868T>C) is classified Uncertain significance in CCDC125 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.0771); Very rare (popmax 0.00891%, eas).

How common is CCDC125 p.Ser290Pro (c.868T>C) in the general population?

CCDC125 p.Ser290Pro (c.868T>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CCDC125 p.Ser290Pro (c.868T>C)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

CCDC125 p.Ser290Pro

c.868T>C · rs752089702 · VCV3138321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -8.77	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 0.76	GERP -1, phastCons 0.016
Regional constraint	o/e 0.95	unconstrained · MANE · 38 kb · p 0.18 · regional, not allelic
Overall
CADD	11.24	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 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000274% 4/1,461,886 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: CCDC125
Protein: p.Ser290Pro
Coding: c.868T>C
MANE Select: NM_176816
dbSNP: rs752089702
Type: single nucleotide variant
Location: chr5:69294849 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.24

Full CCDC125 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC125 p.Ala244Thr Uncertain significance ★ ⚠ same type
CCDC125 p.Ala274Val Uncertain significance ★ ⚠ same type
CCDC125 p.Ala295Val Uncertain significance ★ ⚠ same type
CCDC125 p.Ala431Thr Uncertain significance ★ ⚠ same type
CCDC125 p.Ala72Val Uncertain significance ★ ⚠ same type
CCDC125 p.Arg336Lys Uncertain significance ★ ⚠ same type
CCDC125 p.Arg430Gln Uncertain significance ★ ⚠ same type
CCDC125 p.Arg459Cys 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/ccdc125-p-ser290pro (accessed [today's date]).

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