Is CCDC82 p.Arg388Cys (c.1162C>T) pathogenic?

CCDC82 p.Arg388Cys (c.1162C>T) is classified Uncertain significance in CCDC82 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.6108); Very rare (popmax 0.000935%, nfe).

How common is CCDC82 p.Arg388Cys (c.1162C>T) in the general population?

CCDC82 p.Arg388Cys (c.1162C>T) is very rare (popmax 0.000935%, nfe) (gnomAD).

What do computational predictors say about CCDC82 p.Arg388Cys (c.1162C>T)?

AlphaMissense predicts likely pathogenic (score 0.6108) — an in-silico prediction, not a clinical call.

CCDC82 p.Arg388Cys

c.1162C>T · VCV4649718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000935%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6108	likely pathogenic
REVEL	0.31	indeterminate
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 31 kb · p 0.074 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000935% European (non-Finnish) · 11/1,176,888 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000756% 11/1,454,586 alleles · very rare

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.Arg388Cys
Coding: c.1162C>T
MANE Select: NM_024725
Type: single nucleotide variant
Location: chr11:96371060 (GRCh38)
Gene constraint: LOEUF 1.06 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.94

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

Similar variants

CCDC82 p.Arg388His 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
CCDC82 p.Arg179Ter Conflicting classifications of pathogenicity ★ 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-arg388cys (accessed [today's date]).

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