Is CCDC83 p.Glu41Asp (c.123G>C) pathogenic?

CCDC83 p.Glu41Asp (c.123G>C) is classified Uncertain significance in CCDC83 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.3218); Very rare (popmax 0.00964%, afr).

How common is CCDC83 p.Glu41Asp (c.123G>C) in the general population?

CCDC83 p.Glu41Asp (c.123G>C) is very rare (popmax 0.00964%, afr) (gnomAD).

What do computational predictors say about CCDC83 p.Glu41Asp (c.123G>C)?

AlphaMissense predicts likely benign (score 0.3218) — an in-silico prediction, not a clinical call.

CCDC83 p.Glu41Asp

c.123G>C · rs764146289 · VCV3139458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3218 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00964%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3218	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -6.84	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 1.5	GERP -2.4, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 54 kb · p 0.043 · regional, not allelic
Overall
CADD	14.12	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 0.00964% African / African-American · 7/72,616 alleles

Filtering AF 0.0045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00317%

Overall 0.000449% 7/1,559,734 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: CCDC83
Protein: p.Glu41Asp
Coding: c.123G>C
MANE Select: NM_001286159
dbSNP: rs764146289
Type: single nucleotide variant
Location: chr11:85873238 (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-glu41asp (accessed [today's date]).

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