Is CCDC68 p.Lys98Arg (c.293A>G) pathogenic?

CCDC68 p.Lys98Arg (c.293A>G) is classified Uncertain significance in CCDC68 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely benign (0.1042); Ultra-rare (popmax 0.0134%, eas).

How common is CCDC68 p.Lys98Arg (c.293A>G) in the general population?

CCDC68 p.Lys98Arg (c.293A>G) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CCDC68 p.Lys98Arg (c.293A>G)?

AlphaMissense predicts likely benign (score 0.1042) — an in-silico prediction, not a clinical call.

CCDC68 p.Lys98Arg

c.293A>G · VCV3828736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1042 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1042	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -7.78	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 6.1	GERP 2.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.29 · regional, not allelic
Overall
CADD	23.2	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 0.0134% East Asian · 6/44,826 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000434% 7/1,613,556 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,471
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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: CCDC68
Protein: p.Lys98Arg
Coding: c.293A>G
MANE Select: NM_025214
Type: single nucleotide variant
Location: chr18:54938009 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 81.20

Full CCDC68 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC68 p.Arg13Gly Uncertain significance ★ ⚠ same type
CCDC68 p.Arg208Ile Uncertain significance ★ ⚠ same type
CCDC68 p.Arg258Cys Uncertain significance ★ ⚠ same type
CCDC68 p.Arg258Gly Uncertain significance ★ ⚠ same type
CCDC68 p.Arg258His Uncertain significance ★ ⚠ same type
CCDC68 p.Arg258Ser Uncertain significance ★ ⚠ same type
CCDC68 p.Arg41Gln Uncertain significance ★ ⚠ same type
CCDC68 p.Arg41Leu 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/ccdc68-p-lys98arg (accessed [today's date]).

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