Is CDC42SE2 p.Ser52Pro (c.154T>C) pathogenic?

CDC42SE2 p.Ser52Pro (c.154T>C) is classified Uncertain significance in CDC42SE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). AlphaMissense: ambiguous (0.4187); Absent from gnomAD v4.1.

How common is CDC42SE2 p.Ser52Pro (c.154T>C) in the general population?

CDC42SE2 p.Ser52Pro (c.154T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC42SE2 p.Ser52Pro (c.154T>C)?

AlphaMissense predicts ambiguous (score 0.4187) — an in-silico prediction, not a clinical call.

CDC42SE2 p.Ser52Pro

c.154T>C · VCV3998618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4187 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4187	ambiguous
REVEL	0.248	benign-leaning
SaProt	LLR -6.82	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 32 kb · p 0.017 · regional, not allelic
Overall
CADD	25.8	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

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: CDC42SE2
Protein: p.Ser52Pro
Coding: c.154T>C
MANE Select: NM_001375635
Type: single nucleotide variant
Location: chr5:131385642 (GRCh38)
Gene constraint: LOEUF 1.407 · pLI 0.52 (gnomAD)
Structure: AlphaFold pLDDT 68.02
Residue 52: a modified residue (phosphoserine)

Full CDC42SE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC42SE2 p.Ala72Pro Uncertain significance ★ ⚠ same type
CDC42SE2 p.Arg22Gln Uncertain significance ★ ⚠ same type
CDC42SE2 p.Asn58Tyr Uncertain significance ★ ⚠ same type
CDC42SE2 p.Gln15His Uncertain significance ★ ⚠ same type
CDC42SE2 p.Ile56Leu Uncertain significance ★ ⚠ same type
CDC42SE2 p.Leu78His Uncertain significance ★ ⚠ same type
CDC42SE2 p.Phe4Tyr Uncertain significance ★ ⚠ same type
CDC42SE2 p.Ser43Leu 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/cdc42se2-p-ser52pro (accessed [today's date]).

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