Is CCDC82 p.Arg431His (c.1292G>A) pathogenic?

CCDC82 p.Arg431His (c.1292G>A) is classified Uncertain significance in CCDC82 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: likely pathogenic (0.6627); Very rare (popmax 0.00535%, afr).

How common is CCDC82 p.Arg431His (c.1292G>A) in the general population?

CCDC82 p.Arg431His (c.1292G>A) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about CCDC82 p.Arg431His (c.1292G>A)?

AlphaMissense predicts likely pathogenic (score 0.6627) — an in-silico prediction, not a clinical call.

CCDC82 p.Arg431His

c.1292G>A · VCV4221612

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6627	likely pathogenic
REVEL	0.25	benign-leaning
SaProt	LLR -11.01	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 31 kb · p 0.074 · regional, not allelic
Overall
CADD	26.3	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 0.00535% African / African-American · 4/74,800 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00106% 17/1,608,966 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,700
East Asian	0.00447%	22,363
Admixed American	0.00334%	29,925
Remaining individualsnot grpmax-eligible	0.00161%	62,252
South Asian	0.00111%	89,774
European (non-Finnish)	0.000595%	168,193

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.Arg431His
Coding: c.1292G>A
MANE Select: NM_024725
Type: single nucleotide variant
Location: chr11:96365068 (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-arg431his (accessed [today's date]).

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