Is SRD5A2 p.Pro30Ser (c.88C>T) pathogenic?

SRD5A2 p.Pro30Ser (c.88C>T) is classified Uncertain significance in SRD5A2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.1791); Absent from gnomAD v4.1; Associated with 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency.

What condition is associated with SRD5A2 p.Pro30Ser (c.88C>T)?

SRD5A2 p.Pro30Ser (c.88C>T) is associated with 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency (ClinVar).

How common is SRD5A2 p.Pro30Ser (c.88C>T) in the general population?

SRD5A2 p.Pro30Ser (c.88C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRD5A2 p.Pro30Ser (c.88C>T)?

AlphaMissense predicts likely benign (score 0.1791) — an in-silico prediction, not a clinical call.

SRD5A2 p.Pro30Ser

Q: How is 46,XY difference of sex development due to 5-alpha-reductase 2 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.88C>T · VCV3367170

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1791 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency

Computational evidence

Protein change
AlphaMissense	0.1791	likely benign
SaProt	LLR -1.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 2.2, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 55 kb · p 0.17 · regional, not allelic
Overall
CADD	20.2	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; SaProt is an independent agreement signal.

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: SRD5A2
Protein: p.Pro30Ser
Coding: c.88C>T
MANE Select: NM_000348
Type: single nucleotide variant
Location: chr2:31580813 (GRCh38)
Gene constraint: LOEUF 1.717 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.56 · 1 PDB
Residue 30: a UniProt-annotated variant site (found in individual with micropenis); a UniProt-annotated variant site (increased affinity for testosterone; increased affinity for nadph; decreased vmax)

Full SRD5A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 46,XY difference of sex development due to 5-alpha-reductase 2 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

SRD5A2 c.282-2A>G Pathogenic ★★ same condition
SRD5A2 c.698+1G>T Pathogenic/Likely pathogenic ★★ same condition
SRD5A2 p.Ala207Asp Pathogenic/Likely pathogenic ★★ same condition
SRD5A2 p.Ala228Thr Pathogenic/Likely pathogenic ★★ same condition
SRD5A2 p.Ala65Pro Pathogenic/Likely pathogenic ★★ same condition
SRD5A2 p.Arg103Ter Pathogenic ★★ same condition
SRD5A2 p.Arg145Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
SRD5A2 p.Arg227Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition

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/srd5a2-p-pro30ser (accessed [today's date]).

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