Is CCDC83 p.Ser80Arg (c.240T>A) pathogenic?

CCDC83 p.Ser80Arg (c.240T>A) is classified Uncertain significance in CCDC83 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.2248); Ultra-rare (popmax 0.0317%, amr).

How common is CCDC83 p.Ser80Arg (c.240T>A) in the general population?

CCDC83 p.Ser80Arg (c.240T>A) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about CCDC83 p.Ser80Arg (c.240T>A)?

AlphaMissense predicts likely benign (score 0.2248) — an in-silico prediction, not a clinical call.

CCDC83 p.Ser80Arg

c.240T>A · rs201110814 · VCV2455603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2248 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2248	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.74	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 -2.9	GERP -2.5
Regional constraint	o/e 1.09	unconstrained · MANE · 54 kb · p 0.043 · regional, not allelic
Overall
CADD	4.45	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 0.0317% Admixed American · 19/59,954 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00502% 81/1,613,466 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,155
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0128%	7,810
European (non-Finnish)	0.00432%	23,133
African / African-American	0.00134%	74,766
South Asian	0.0011%	91,056

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.Ser80Arg
Coding: c.240T>A
MANE Select: NM_001286159
dbSNP: rs201110814
Type: single nucleotide variant
Location: chr11:85882572 (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-ser80arg (accessed [today's date]).

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