Is CCDC68 p.Ser303Cys (c.908C>G) pathogenic?

CCDC68 p.Ser303Cys (c.908C>G) is classified Uncertain significance in CCDC68 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.0906); Very rare (popmax 0.00902%, nfe).

How common is CCDC68 p.Ser303Cys (c.908C>G) in the general population?

CCDC68 p.Ser303Cys (c.908C>G) is very rare (popmax 0.00902%, nfe) (gnomAD).

What do computational predictors say about CCDC68 p.Ser303Cys (c.908C>G)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

CCDC68 p.Ser303Cys

c.908C>G · rs150354176 · VCV3139304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00902%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 6.4	GERP 0.96, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.29 · regional, not allelic
Overall
CADD	22.4	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 0.00902% European (non-Finnish) · 106/1,175,406 alleles

Filtering AF 0.0076% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00709%

Overall 0.00684% 110/1,608,866 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00902%	11,089
Remaining individualsnot grpmax-eligible	0.00321%	31,138
African / African-American	0.00267%	37,407

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.Ser303Cys
Coding: c.908C>G
MANE Select: NM_025214
dbSNP: rs150354176
Type: single nucleotide variant
Location: chr18:54907828 (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-ser303cys (accessed [today's date]).

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