Is CSDC2 p.Pro50Ala (c.148C>G) pathogenic?

CSDC2 p.Pro50Ala (c.148C>G) is classified Uncertain significance in CSDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.9165); Absent from gnomAD v4.1.

How common is CSDC2 p.Pro50Ala (c.148C>G) in the general population?

CSDC2 p.Pro50Ala (c.148C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSDC2 p.Pro50Ala (c.148C>G)?

AlphaMissense predicts likely pathogenic (score 0.9165) — an in-silico prediction, not a clinical call.

CSDC2 p.Pro50Ala

c.148C>G · VCV3497504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9165 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9165	likely pathogenic
REVEL	0.254	benign-leaning
SaProt	LLR -11.92	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,926 bp · p 0.21 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSDC2
Protein: p.Pro50Ala
Coding: c.148C>G
MANE Select: NM_014460
Type: single nucleotide variant
Location: chr22:41572113 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82
Residue 50: the 'disordered' region

Full CSDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSDC2 p.Arg33Ser Uncertain significance ★ same type
CSDC2 p.Arg37Gln Uncertain significance ★ ⚠ same type
CSDC2 p.Arg43Gln Uncertain significance ★ ⚠ same type
CSDC2 p.Arg43Trp Uncertain significance ★ ⚠ same type
CSDC2 p.Arg55Thr Uncertain significance ★ ⚠ same type
CSDC2 p.Arg78Cys Uncertain significance ★ ⚠ same type
CSDC2 p.Asp111Gly Uncertain significance ★ ⚠ same type
CSDC2 p.Glu30Lys 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/csdc2-p-pro50ala (accessed [today's date]).

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