Is CCDC68 p.Arg258Cys (c.772C>T) pathogenic?

CCDC68 p.Arg258Cys (c.772C>T) is classified Uncertain significance in CCDC68 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.1168); Very rare (popmax 0.00879%, sas).

How common is CCDC68 p.Arg258Cys (c.772C>T) in the general population?

CCDC68 p.Arg258Cys (c.772C>T) is very rare (popmax 0.00879%, sas) (gnomAD).

What do computational predictors say about CCDC68 p.Arg258Cys (c.772C>T)?

AlphaMissense predicts likely benign (score 0.1168) — an in-silico prediction, not a clinical call.

CCDC68 p.Arg258Cys

c.772C>T · rs771391383 · VCV3139303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1168 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00879%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1168	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -6.42	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 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.29 · regional, not allelic
Overall
CADD	25.0	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 0.00879% South Asian · 8/91,064 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00465% 75/1,613,060 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00879%	11,383
Remaining individualsnot grpmax-eligible	0.0064%	15,613
Admixed American	0.005%	19,998
European (non-Finnish)	0.00475%	21,057
African / African-American	0.00401%	24,963
East Asian	0.00223%	44,892

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.Arg258Cys
Coding: c.772C>T
MANE Select: NM_025214
dbSNP: rs771391383
Type: single nucleotide variant
Location: chr18:54919288 (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.Arg258Gly Uncertain significance ★ ⚠ same residue
CCDC68 p.Arg258His Uncertain significance ★ ⚠ same residue
CCDC68 p.Arg258Ser Uncertain significance ★ ⚠ same residue
CCDC68 p.Arg13Gly Uncertain significance ★ ⚠ same type
CCDC68 p.Arg208Ile 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-arg258cys (accessed [today's date]).

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