Is CCDC80 p.Arg776Trp (c.2326C>T) pathogenic?

CCDC80 p.Arg776Trp (c.2326C>T) is classified Uncertain significance in CCDC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely pathogenic (0.7666); Ultra-rare (popmax 0.0357%, eas).

How common is CCDC80 p.Arg776Trp (c.2326C>T) in the general population?

CCDC80 p.Arg776Trp (c.2326C>T) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

What do computational predictors say about CCDC80 p.Arg776Trp (c.2326C>T)?

AlphaMissense predicts likely pathogenic (score 0.7666) — an in-silico prediction, not a clinical call.

CCDC80 p.Arg776Trp

c.2326C>T · rs750720921 · VCV2595938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7666	likely pathogenic
REVEL	0.431	indeterminate
SaProt	LLR -11.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 34 kb · p 0.85 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0357% East Asian · 16/44,860 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00205% 33/1,612,406 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,804
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Admixed American	0.00334%	29,969
South Asian	0.0022%	45,508
European (non-Finnish)	0.00102%	98,310

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.Arg776Trp
Coding: c.2326C>T
MANE Select: NM_199511
dbSNP: rs750720921
Type: single nucleotide variant
Location: chr3:112610077 (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.Arg776Gln Uncertain significance ★ ⚠ same residue
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

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-arg776trp (accessed [today's date]).

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