Is CCDC69 p.Arg55Gln (c.164G>A) pathogenic?

CCDC69 p.Arg55Gln (c.164G>A) is classified Likely benign in CCDC69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.0579); Very rare (popmax 0.00668%, afr).

How common is CCDC69 p.Arg55Gln (c.164G>A) in the general population?

CCDC69 p.Arg55Gln (c.164G>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about CCDC69 p.Arg55Gln (c.164G>A)?

AlphaMissense predicts likely benign (score 0.0579) — an in-silico prediction, not a clinical call.

CCDC69 p.Arg55Gln

c.164G>A · VCV3997136

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0579 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0579	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.37	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 -1.3	GERP -1.5
Regional constraint	o/e 1.09	unconstrained · MANE · 41 kb · p 0.1 · regional, not allelic
Overall
CADD	7.543	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 0.00668% African / African-American · 5/74,848 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00316% 51/1,613,398 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,970
Remaining individualsnot grpmax-eligible	0.00641%	15,612
Admixed American	0.00334%	29,967
European (non-Finnish)	0.00314%	31,886
Finnishnot grpmax-eligible	0.00313%	31,992
South Asian	0.0011%	90,952

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.Arg55Gln
Coding: c.164G>A
MANE Select: NM_015621
Type: single nucleotide variant
Location: chr5:151201649 (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.Arg55Trp Uncertain significance ★ ⚠ same residue
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

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-arg55gln (accessed [today's date]).

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