Is CCDC80 p.Arg419Gln (c.1256G>A) pathogenic?

CCDC80 p.Arg419Gln (c.1256G>A) is classified Uncertain significance in CCDC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.0881); Very rare (popmax 0.00669%, eas).

How common is CCDC80 p.Arg419Gln (c.1256G>A) in the general population?

CCDC80 p.Arg419Gln (c.1256G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CCDC80 p.Arg419Gln (c.1256G>A)?

AlphaMissense predicts likely benign (score 0.0881) — an in-silico prediction, not a clinical call.

CCDC80 p.Arg419Gln

c.1256G>A · VCV3264320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0881	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.35	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 2.2	GERP 0.84, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 34 kb · p 0.85 · regional, not allelic
Overall
CADD	22.8	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 0.00669% East Asian · 3/44,864 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00545% 88/1,613,896 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,955
European (non-Finnish)	0.00644%	15,526
Remaining individualsnot grpmax-eligible	0.0048%	20,835
South Asian	0.00439%	22,763
Admixed American	0.00333%	29,998

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.Arg419Gln
Coding: c.1256G>A
MANE Select: NM_199511
Type: single nucleotide variant
Location: chr3:112638650 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.51
Residue 419: the 'disordered' region

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

Similar variants

CCDC80 p.Arg419Trp 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-arg419gln (accessed [today's date]).

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