Is CCDC88C p.Arg697Cys (c.2089C>T) pathogenic?

CCDC88C p.Arg697Cys (c.2089C>T) is classified Uncertain significance in CCDC88C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-20). AlphaMissense: likely benign (0.1649); Ultra-rare (popmax 0.025%, amr); Associated with Inborn genetic diseases.

What condition is associated with CCDC88C p.Arg697Cys (c.2089C>T)?

CCDC88C p.Arg697Cys (c.2089C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CCDC88C p.Arg697Cys (c.2089C>T) in the general population?

CCDC88C p.Arg697Cys (c.2089C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about CCDC88C p.Arg697Cys (c.2089C>T)?

AlphaMissense predicts likely benign (score 0.1649) — an in-silico prediction, not a clinical call.

CCDC88C p.Arg697Cys

c.2089C>T · rs763668804 · VCV2169000

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1649 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1649	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -11.53	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -0.82, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 112 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	25.3	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 0.025% Admixed American · 15/59,980 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00248% 40/1,609,706 alleles · ultra-rare exomes 37/1,457,686 · genomes 3/152,020 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,999
East Asian	0.00223%	44,854
European (non-Finnish)	0.00195%	51,298
South Asian	0.0011%	91,078

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: CCDC88C
Protein: p.Arg697Cys
Coding: c.2089C>T
MANE Select: NM_001080414
dbSNP: rs763668804
Type: single nucleotide variant
Location: chr14:91313727 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.69

Full CCDC88C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCDC88C p.Ala1102Thr Uncertain significance ★★ ⚠ same condition
CCDC88C p.Ala1247Thr Uncertain significance ★★ ⚠ same condition
CCDC88C p.Ala1289Thr Uncertain significance ★★ ⚠ same condition
CCDC88C p.Ala1446Val Uncertain significance ★★ ⚠ same condition
CCDC88C p.Ala1762Thr Uncertain significance ★★ ⚠ same condition
CCDC88C p.Ala1831Thr Uncertain significance ★★ ⚠ same condition
CCDC88C p.Ala1831Val Uncertain significance ★★ ⚠ same condition
CCDC88C p.Ala1995Ser Uncertain significance ★★ ⚠ same condition

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/ccdc88c-p-arg697cys (accessed [today's date]).

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