Is CCDC125 p.Arg97Gln (c.290G>A) pathogenic?

CCDC125 p.Arg97Gln (c.290G>A) is classified Uncertain significance in CCDC125 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0751); Very rare (popmax 0.00223%, eas).

How common is CCDC125 p.Arg97Gln (c.290G>A) in the general population?

CCDC125 p.Arg97Gln (c.290G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CCDC125 p.Arg97Gln (c.290G>A)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

CCDC125 p.Arg97Gln

c.290G>A · VCV4648991

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.8	GERP -3.5
Regional constraint	o/e 0.95	unconstrained · MANE · 38 kb · p 0.18 · regional, not allelic
Overall
CADD	11.61	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 0.00223% East Asian · 1/44,890 alleles

Overall 0.000248% 4/1,613,088 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
Admixed American	0.00167%	59,878
South Asian	0.0011%	90,990
European (non-Finnish)	8.48e-05%	1,179,522

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.Arg97Gln
Coding: c.290G>A
MANE Select: NM_176816
Type: single nucleotide variant
Location: chr5:69320251 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.24
Residue 97: the 'disordered' region

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-arg97gln (accessed [today's date]).

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