Is C2CD4C p.Pro48Ser (c.142C>T) pathogenic?

C2CD4C p.Pro48Ser (c.142C>T) is classified Uncertain significance in C2CD4C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely pathogenic (0.9968); Absent from gnomAD v4.1.

How common is C2CD4C p.Pro48Ser (c.142C>T) in the general population?

C2CD4C p.Pro48Ser (c.142C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C2CD4C p.Pro48Ser (c.142C>T)?

AlphaMissense predicts likely pathogenic (score 0.9968) — an in-silico prediction, not a clinical call.

C2CD4C p.Pro48Ser

c.142C>T · rs2512244105 · VCV2331697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9968 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,463,142)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9968	likely pathogenic · top 1% in C2CD4C
REVEL	0.7	pathogenic-leaning
SaProt	LLR -12.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 1,262 bp · p 0.088 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,463,142). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C2CD4C
Protein: p.Pro48Ser
Coding: c.142C>T
MANE Select: NM_001136263
dbSNP: rs2512244105
Type: single nucleotide variant
Location: chr19:408220 (GRCh38)
Gene constraint: LOEUF 1.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.88
Residue 48: the 'disordered' region

Full C2CD4C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD4C p.Ala107Thr Uncertain significance ★ ⚠ same type
C2CD4C p.Ala151Ser Uncertain significance ★ ⚠ same type
C2CD4C p.Ala154Ser Uncertain significance ★ ⚠ same type
C2CD4C p.Ala181Pro Uncertain significance ★ ⚠ same type
C2CD4C p.Ala187Val Uncertain significance ★ ⚠ same type
C2CD4C p.Ala203Val Uncertain significance ★ ⚠ same type
C2CD4C p.Ala248Thr Uncertain significance ★ ⚠ same type
C2CD4C p.Ala265Val 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/c2cd4c-p-pro48ser (accessed [today's date]).

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