Is CCDC88A p.Gln232Arg (c.695A>G) pathogenic?

CCDC88A p.Gln232Arg (c.695A>G) is classified Uncertain significance in CCDC88A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-04). AlphaMissense: likely benign (0.1131); Ultra-rare (popmax 0.0164%, mid).

How common is CCDC88A p.Gln232Arg (c.695A>G) in the general population?

CCDC88A p.Gln232Arg (c.695A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CCDC88A p.Gln232Arg (c.695A>G)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

CCDC88A p.Gln232Arg

c.695A>G · rs144507962 · VCV1924364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 62 kb · p 2.8e-11 · regional, not allelic
Overall
CADD	24.7	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.000424%	235,987

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: CCDC88A
Protein: p.Gln232Arg
Coding: c.695A>G
MANE Select: NM_001365480
dbSNP: rs144507962
Type: single nucleotide variant
Location: chr2:55355684 (GRCh38)
Gene constraint: LOEUF 0.25 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.09 · 1 PDB

Full CCDC88A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC88A p.Gln232= Likely benign ★ same residue
CCDC88A p.Ala1536Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala155Val Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala158Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala1770Val Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala194Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala72Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala845Gly 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/ccdc88a-p-gln232arg (accessed [today's date]).

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