Is CCDC50 p.Gln57His (c.171G>C) pathogenic?

CCDC50 p.Gln57His (c.171G>C) is classified Uncertain significance in CCDC50 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: likely benign (0.2391); Very rare (popmax 0.000254%, nfe); Associated with CCDC50-related disorder.

What condition is associated with CCDC50 p.Gln57His (c.171G>C)?

CCDC50 p.Gln57His (c.171G>C) is associated with CCDC50-related disorder (ClinVar).

How common is CCDC50 p.Gln57His (c.171G>C) in the general population?

CCDC50 p.Gln57His (c.171G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CCDC50 p.Gln57His (c.171G>C)?

AlphaMissense predicts likely benign (score 0.2391) — an in-silico prediction, not a clinical call.

CCDC50 p.Gln57His

c.171G>C · rs1260207759 · VCV2632482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2391 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCDC50-related disorder

Computational evidence

Protein change
AlphaMissense	0.2391	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 62 kb · p 0.39 · regional, not allelic
Overall
CADD	23.7	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) · 3/1,179,942 alleles

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

Overall 0.000205% 3/1,461,764 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.Gln57His
Coding: c.171G>C
MANE Select: NM_178335
dbSNP: rs1260207759
Type: single nucleotide variant
Location: chr3:191358056 (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

Disease context

CCDC50-related disorder

Similar variants

CCDC50 p.Glu412Lys Uncertain significance ★★ ⚠ same condition
CCDC50 c.448+5C>G Likely benign same condition
CCDC50 p.Arg263Pro Likely benign same condition
CCDC50 p.Ile381= Likely benign same condition
CCDC50 c.977-7_977-5dup Benign same condition
CCDC50 p.Ala453Val Uncertain significance ★★ ⚠ same type
CCDC50 p.Arg138Pro Uncertain significance ★★ ⚠ same type
CCDC50 p.Arg227Gln 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-gln57his (accessed [today's date]).

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