Is CCDC68 p.Arg208Ile (c.623G>T) pathogenic?

CCDC68 p.Arg208Ile (c.623G>T) is classified Uncertain significance in CCDC68 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.2191); Absent from gnomAD v4.1.

How common is CCDC68 p.Arg208Ile (c.623G>T) in the general population?

CCDC68 p.Arg208Ile (c.623G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC68 p.Arg208Ile (c.623G>T)?

AlphaMissense predicts likely benign (score 0.2191) — an in-silico prediction, not a clinical call.

CCDC68 p.Arg208Ile

c.623G>T · rs2511696917 · VCV3139299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2191 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2191	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -7.22	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 1.1	GERP -3.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.29 · regional, not allelic
Overall
CADD	19.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC68
Protein: p.Arg208Ile
Coding: c.623G>T
MANE Select: NM_025214
dbSNP: rs2511696917
Type: single nucleotide variant
Location: chr18:54928860 (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.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
CCDC68 p.Asn292Lys 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-arg208ile (accessed [today's date]).

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