Is CCDC80 p.Pro157Ser (c.469C>T) pathogenic?

CCDC80 p.Pro157Ser (c.469C>T) is classified Uncertain significance in CCDC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: ambiguous (0.5413); Very rare (popmax 0.000254%, nfe).

How common is CCDC80 p.Pro157Ser (c.469C>T) in the general population?

CCDC80 p.Pro157Ser (c.469C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CCDC80 p.Pro157Ser (c.469C>T)?

AlphaMissense predicts ambiguous (score 0.5413) — an in-silico prediction, not a clinical call.

CCDC80 p.Pro157Ser

c.469C>T · VCV4649704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5413	ambiguous
REVEL	0.839	moderately pathogenic-leaning
SaProt	LLR -9.96	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 34 kb · p 0.85 · regional, not allelic
Overall
CADD	27.8	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 0.000254% European (non-Finnish) · 3/1,180,026 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)grpmax	0.000254%	393,342

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro157Ser
Coding: c.469C>T
MANE Select: NM_199511
Type: single nucleotide variant
Location: chr3:112639437 (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-pro157ser (accessed [today's date]).

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