Is CCDC50 p.Pro431Thr (c.1291C>A) pathogenic?

CCDC50 p.Pro431Thr (c.1291C>A) is classified Uncertain significance in CCDC50 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-28). AlphaMissense: likely benign (0.0597); Very rare (popmax 0.00223%, eas).

How common is CCDC50 p.Pro431Thr (c.1291C>A) in the general population?

CCDC50 p.Pro431Thr (c.1291C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CCDC50 p.Pro431Thr (c.1291C>A)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

CCDC50 p.Pro431Thr

c.1291C>A · rs139060348 · VCV618553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -6.05	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 -0.17	GERP -5.4
Regional constraint	o/e 0.96	unconstrained · MANE · 62 kb · p 0.39 · regional, not allelic
Overall
CADD	7.456	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P255T vs ClinVar P431T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,832 alleles

Overall 6.85e-05% 1/1,460,782 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: CCDC50
Protein: p.Pro431Thr
Coding: c.1291C>A
MANE Select: NM_178335
dbSNP: rs139060348
Type: single nucleotide variant
Location: chr3:191382794 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.90 · 1 PDB

Full CCDC50 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC50 p.Pro431Ser Uncertain significance ★ ⚠ same residue
CCDC50 p.Ala453Val Uncertain significance ★★ ⚠ same type
CCDC50 p.Arg138Pro Uncertain significance ★★ ⚠ same type
CCDC50 p.Arg227Gln Uncertain significance ★★ same type
CCDC50 p.Arg227Trp Uncertain significance ★★ same type
CCDC50 p.Arg270Ter Uncertain significance ★★ same type
CCDC50 p.Arg274Ter Uncertain significance ★★ same type
CCDC50 p.Arg305Thr 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/ccdc50-p-pro431thr (accessed [today's date]).

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