Is CCDC82 p.Arg23Gln (c.68G>A) pathogenic?

CCDC82 p.Arg23Gln (c.68G>A) is classified Uncertain significance in CCDC82 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.1636); Very rare (popmax 0.0033%, sas).

How common is CCDC82 p.Arg23Gln (c.68G>A) in the general population?

CCDC82 p.Arg23Gln (c.68G>A) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about CCDC82 p.Arg23Gln (c.68G>A)?

AlphaMissense predicts likely benign (score 0.1636) — an in-silico prediction, not a clinical call.

CCDC82 p.Arg23Gln

c.68G>A · VCV4221603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1636 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1636	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.62	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 4	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 31 kb · p 0.074 · regional, not allelic
Overall
CADD	20.6	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 0.0033% South Asian · 3/90,920 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000558% 9/1,613,056 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,307
Remaining individualsnot grpmax-eligible	0.0016%	62,444
European (non-Finnish)	0.000424%	235,914

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.Arg23Gln
Coding: c.68G>A
MANE Select: NM_024725
Type: single nucleotide variant
Location: chr11:96384680 (GRCh38)
Gene constraint: LOEUF 1.06 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.94
Residue 23: the 'disordered' region

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

Similar variants

CCDC82 p.Arg23Ter Likely pathogenic ★ same residue
CCDC82 p.Thr108Ala Benign ★★ 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
CCDC82 p.Arg211Cys 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-arg23gln (accessed [today's date]).

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