Is CCDC69 p.Arg87Gln (c.260G>A) pathogenic?

CCDC69 p.Arg87Gln (c.260G>A) is classified Likely benign in CCDC69 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.0667); Ultra-rare (popmax 0.0165%, mid).

How common is CCDC69 p.Arg87Gln (c.260G>A) in the general population?

CCDC69 p.Arg87Gln (c.260G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CCDC69 p.Arg87Gln (c.260G>A)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

CCDC69 p.Arg87Gln

c.260G>A · VCV3486851

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.20	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 -6.8	GERP -4.2
Regional constraint	o/e 1.09	unconstrained · MANE · 41 kb · p 0.1 · regional, not allelic
Overall
CADD	0.009	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00123% 18/1,461,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
East Asian	0.0134%	7,480
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000847%	117,999

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: CCDC69
Protein: p.Arg87Gln
Coding: c.260G>A
MANE Select: NM_015621
Type: single nucleotide variant
Location: chr5:151199056 (GRCh38)
Gene constraint: LOEUF 1.181 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.55

Full CCDC69 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC69 p.Ala110Thr Uncertain significance ★ ⚠ same type
CCDC69 p.Ala118Glu Uncertain significance ★ ⚠ same type
CCDC69 p.Ala118Thr Uncertain significance ★ ⚠ same type
CCDC69 p.Ala118Val Uncertain significance ★ ⚠ same type
CCDC69 p.Ala75Val Uncertain significance ★ ⚠ same type
CCDC69 p.Arg191Cys Uncertain significance ★ ⚠ same type
CCDC69 p.Arg191His Uncertain significance ★ ⚠ same type
CCDC69 p.Arg198Gln 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/ccdc69-p-arg87gln (accessed [today's date]).

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