Is CCDC83 p.Arg63His (c.188G>A) pathogenic?

CCDC83 p.Arg63His (c.188G>A) is classified Uncertain significance in CCDC83 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.0757); Very rare (popmax 0.00659%, sas).

How common is CCDC83 p.Arg63His (c.188G>A) in the general population?

CCDC83 p.Arg63His (c.188G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about CCDC83 p.Arg63His (c.188G>A)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

CCDC83 p.Arg63His

c.188G>A · VCV3264327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.26	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1	GERP 0.7, phastCons 0.66
Regional constraint	o/e 1.09	unconstrained · MANE · 54 kb · p 0.043 · regional, not allelic
Overall
CADD	9.404	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 0.00659% South Asian · 6/90,996 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00291% 47/1,613,180 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,166
Admixed American	0.00334%	29,921
European (non-Finnish)	0.00314%	31,882
East Asian	0.00223%	44,866
Finnishnot grpmax-eligible	0.00156%	63,992

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: CCDC83
Protein: p.Arg63His
Coding: c.188G>A
MANE Select: NM_001286159
Type: single nucleotide variant
Location: chr11:85882520 (GRCh38)
Gene constraint: LOEUF 1.263 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.76

Full CCDC83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC83 c.794+1269C>G Uncertain significance ★ same type
CCDC83 c.794+1294T>C Uncertain significance ★ same type
CCDC83 c.794+1326G>A Uncertain significance ★ same type
CCDC83 c.794+1332C>T Uncertain significance ★ same type
CCDC83 p.Ala149Val Uncertain significance ★ ⚠ same type
CCDC83 p.Ala166Thr Uncertain significance ★ ⚠ same type
CCDC83 p.Ala39Gly Uncertain significance ★ ⚠ same type
CCDC83 p.Ala98Val 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/ccdc83-p-arg63his (accessed [today's date]).

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