Is CCDC80 p.Val845Ile (c.2533G>A) pathogenic?

CCDC80 p.Val845Ile (c.2533G>A) is classified Likely benign in CCDC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely benign (0.057); Ultra-rare (popmax 0.033%, mid).

How common is CCDC80 p.Val845Ile (c.2533G>A) in the general population?

CCDC80 p.Val845Ile (c.2533G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CCDC80 p.Val845Ile (c.2533G>A)?

AlphaMissense predicts likely benign (score 0.057) — an in-silico prediction, not a clinical call.

CCDC80 p.Val845Ile

c.2533G>A · rs758154245 · VCV2412395

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.057	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.54	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 -0.18	GERP -4.3
Regional constraint	o/e 1.01	unconstrained · MANE · 34 kb · p 0.85 · regional, not allelic
Overall
CADD	10.18	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.0018% 29/1,613,908 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0165%	6,070
Finnishnot grpmax-eligible	0.00469%	21,338
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000678%	147,484

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.Val845Ile
Coding: c.2533G>A
MANE Select: NM_199511
dbSNP: rs758154245
Type: single nucleotide variant
Location: chr3:112605737 (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-val845ile (accessed [today's date]).

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