Is CCDC82 p.Arg255Cys (c.763C>T) pathogenic?

CCDC82 p.Arg255Cys (c.763C>T) is classified Uncertain significance in CCDC82 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely benign (0.0989); Ultra-rare (popmax 0.0759%, nfe).

How common is CCDC82 p.Arg255Cys (c.763C>T) in the general population?

CCDC82 p.Arg255Cys (c.763C>T) is ultra-rare (popmax 0.0759%, nfe) (gnomAD).

What do computational predictors say about CCDC82 p.Arg255Cys (c.763C>T)?

AlphaMissense predicts likely benign (score 0.0989) — an in-silico prediction, not a clinical call.

CCDC82 p.Arg255Cys

c.763C>T · rs148541924 · VCV3139454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0989 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0759%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0989	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -9.99	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 0.35	GERP -1.6
Regional constraint	o/e 0.93	unconstrained · MANE · 31 kb · p 0.074 · regional, not allelic
Overall
CADD	18.21	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 0.0759% European (non-Finnish) · 895/1,179,312 alleles

Filtering AF 0.0717% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0701%

Overall 0.0609% 982/1,612,524 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0759%	1,318
Remaining individualsnot grpmax-eligible	0.0609%	1,643
Middle Eastern	0.0495%	2,021
African / African-American	0.0227%	4,402
South Asian	0.0209%	4,781
Admixed American	0.0117%	8,541
East Asian	0.00669%	14,953

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: CCDC82
Protein: p.Arg255Cys
Coding: c.763C>T
MANE Select: NM_024725
dbSNP: rs148541924
Type: single nucleotide variant
Location: chr11:96383985 (GRCh38)
Gene constraint: LOEUF 1.06 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.94
Residue 255: the 'disordered' region

Full CCDC82 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC82 p.Arg255His Uncertain significance ★ ⚠ same residue
CCDC82 p.Arg255Leu Uncertain significance ★ ⚠ same residue
CCDC82 p.Thr108Ala Benign ★★ same type
CCDC82 p.Arg23Ter Likely pathogenic ★ same type
CCDC82 p.Ala233Thr Uncertain significance ★ ⚠ same type
CCDC82 p.Ala351Thr Uncertain significance ★ ⚠ same type
CCDC82 p.Arg11Gly Uncertain significance ★ ⚠ same type
CCDC82 p.Arg179Gln 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/ccdc82-p-arg255cys (accessed [today's date]).

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