Is CCDC69 p.Arg191His (c.572G>A) pathogenic?

CCDC69 p.Arg191His (c.572G>A) is classified Uncertain significance in CCDC69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0853); Very rare (popmax 0.004%, afr).

How common is CCDC69 p.Arg191His (c.572G>A) in the general population?

CCDC69 p.Arg191His (c.572G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CCDC69 p.Arg191His (c.572G>A)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

CCDC69 p.Arg191His

c.572G>A · VCV4649619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -9.18	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 -1.2, phastCons 0.21
Regional constraint	o/e 1.09	unconstrained · MANE · 41 kb · p 0.1 · regional, not allelic
Overall
CADD	18.47	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 0.004% African / African-American · 3/74,944 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00316% 51/1,613,832 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,981
European (non-Finnish)	0.00373%	26,814
East Asian	0.00223%	44,886
Admixed American	0.00167%	59,994
Remaining individualsnot grpmax-eligible	0.0016%	62,470
South Asian	0.0011%	91,086

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.Arg191His
Coding: c.572G>A
MANE Select: NM_015621
Type: single nucleotide variant
Location: chr5:151185465 (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.Arg191Cys 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.Arg198Gln Uncertain significance ★ ⚠ same type
CCDC69 p.Arg229Gln 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-arg191his (accessed [today's date]).

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