Is CCDC82 p.Ser470Arg (c.1408A>C) pathogenic?

CCDC82 p.Ser470Arg (c.1408A>C) is classified Uncertain significance in CCDC82 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: ambiguous (0.3643); Ultra-rare (popmax 0.0469%, nfe).

How common is CCDC82 p.Ser470Arg (c.1408A>C) in the general population?

CCDC82 p.Ser470Arg (c.1408A>C) is ultra-rare (popmax 0.0469%, nfe) (gnomAD).

What do computational predictors say about CCDC82 p.Ser470Arg (c.1408A>C)?

AlphaMissense predicts ambiguous (score 0.3643) — an in-silico prediction, not a clinical call.

CCDC82 p.Ser470Arg

c.1408A>C · rs143699327 · VCV2565576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3643 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0469%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3643	ambiguous
REVEL	0.016	strongly benign-leaning
SaProt	LLR -3.21	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -3.6
Regional constraint	o/e 0.93	unconstrained · MANE · 31 kb · p 0.074 · regional, not allelic
Overall
CADD	0.012	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 0.0469% European (non-Finnish) · 549/1,170,650 alleles

Filtering AF 0.0436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0423%

Overall 0.0366% 579/1,582,406 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0469%	2,132
Remaining individualsnot grpmax-eligible	0.0343%	2,915
Admixed American	0.00781%	12,805
African / African-American	0.00689%	14,523

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.Ser470Arg
Coding: c.1408A>C
MANE Select: NM_024725
dbSNP: rs143699327
Type: single nucleotide variant
Location: chr11:96359151 (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.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
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-ser470arg (accessed [today's date]).

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