Is CCDC80 p.Pro339Ser (c.1015C>T) pathogenic?

CCDC80 p.Pro339Ser (c.1015C>T) is classified Uncertain significance in CCDC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.0658); Very rare (popmax 0.0022%, sas).

How common is CCDC80 p.Pro339Ser (c.1015C>T) in the general population?

CCDC80 p.Pro339Ser (c.1015C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CCDC80 p.Pro339Ser (c.1015C>T)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

CCDC80 p.Pro339Ser

c.1015C>T · rs762997282 · VCV2547628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -5.60	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 0.6	GERP -3.8
Regional constraint	o/e 1.01	unconstrained · MANE · 34 kb · p 0.85 · regional, not allelic
Overall
CADD	2.126	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 0.0022% South Asian · 2/91,064 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,390 alleles · very rare

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.Pro339Ser
Coding: c.1015C>T
MANE Select: NM_199511
dbSNP: rs762997282
Type: single nucleotide variant
Location: chr3:112638891 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.51
Residue 339: the 'disordered' region

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-pro339ser (accessed [today's date]).

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