Is CCDC80 p.Arg642Cys (c.1924C>T) pathogenic?

CCDC80 p.Arg642Cys (c.1924C>T) is classified Uncertain significance in CCDC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-27). AlphaMissense: ambiguous (0.3982); Ultra-rare (popmax 0.045%, amr).

How common is CCDC80 p.Arg642Cys (c.1924C>T) in the general population?

CCDC80 p.Arg642Cys (c.1924C>T) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about CCDC80 p.Arg642Cys (c.1924C>T)?

AlphaMissense predicts ambiguous (score 0.3982) — an in-silico prediction, not a clinical call.

CCDC80 p.Arg642Cys

c.1924C>T · rs146397471 · VCV2373486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3982 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Computational evidence

Protein change
AlphaMissense	0.3982	ambiguous
REVEL	0.497	indeterminate
SaProt	LLR -12.00	damaging
Splicing
SpliceAI	Δ0.28	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 4.5	GERP 0.86, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 34 kb · p 0.85 · regional, not allelic
Overall
CADD	29.2	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 0.045% Admixed American · 27/59,976 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.0049% 79/1,613,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,221
African / African-American	0.00401%	24,963
European (non-Finnish)	0.0039%	25,648
Remaining individualsnot grpmax-eligible	0.0032%	31,237
East Asian	0.00223%	44,894

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: CCDC80
Protein: p.Arg642Cys
Coding: c.1924C>T
MANE Select: NM_199511
dbSNP: rs146397471
Type: single nucleotide variant
Location: chr3:112630224 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.51

Full CCDC80 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC80 p.Ala805Val Benign ★★ ⚠ same type
CCDC80 p.His473Tyr Benign ★★ same type
CCDC80 p.Tyr163= Benign ★★ same type
CCDC80 p.Tyr938His Likely benign ★★ ⚠ same type
CCDC80 p.Ala101Val Uncertain significance ★ ⚠ same type
CCDC80 p.Ala110Pro Uncertain significance ★ ⚠ same type
CCDC80 p.Ala110Ser Uncertain significance ★ ⚠ same type
CCDC80 p.Ala125Pro 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/ccdc80-p-arg642cys (accessed [today's date]).

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