Is CCDC88A p.Arg1412= (c.4236G>A) pathogenic?

CCDC88A p.Arg1412= (c.4236G>A) is classified Likely benign in CCDC88A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). Ultra-rare (popmax 0.0433%, amr).

How common is CCDC88A p.Arg1412= (c.4236G>A) in the general population?

CCDC88A p.Arg1412= (c.4236G>A) is ultra-rare (popmax 0.0433%, amr) (gnomAD).

CCDC88A p.Arg1412=

c.4236G>A · rs188147197 · VCV1621785

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0433%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.016	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.001	GERP -3.2, phastCons 0.81
Overall
CADD	5.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0433% Admixed American · 26/60,004 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00161% 26/1,614,018 alleles · ultra-rare

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.Arg1412=
Coding: c.4236G>A
MANE Select: NM_001365480
dbSNP: rs188147197
Type: single nucleotide variant
Location: chr2:55308960 (GRCh38)
Gene constraint: LOEUF 0.25 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.09 · 1 PDB
Residue 1412: the 'disordered' region

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

Similar variants

CCDC88A p.Arg1412Gly Uncertain significance ★ ⚠ 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-arg1412 (accessed [today's date]).

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