Is SRD5A2 p.Phe61= (c.183C>T) pathogenic?

SRD5A2 p.Phe61= (c.183C>T) is classified Likely benign in SRD5A2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-23). Very rare (popmax 0.00167%, amr); Associated with 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency.

What condition is associated with SRD5A2 p.Phe61= (c.183C>T)?

SRD5A2 p.Phe61= (c.183C>T) is associated with 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency (ClinVar).

How common is SRD5A2 p.Phe61= (c.183C>T) in the general population?

SRD5A2 p.Phe61= (c.183C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

SRD5A2 p.Phe61=

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.183C>T · rs61750385 · VCV97394

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.4, phastCons 0.85
Overall
CADD	7.958	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,872 alleles

Overall 0.000311% 5/1,606,580 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,150
Admixed Americangrpmax	0.00167%	59,872
African / African-American	0.00133%	74,920
European (non-Finnish)	8.48e-05%	1,179,270

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SRD5A2
Protein: p.Phe61=
Coding: c.183C>T
MANE Select: NM_000348
dbSNP: rs61750385
Type: single nucleotide variant
Location: chr2:31580718 (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 61: an α-helix; a UniProt-annotated variant site (found in individual with micropenis)

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-phe61 (accessed [today's date]).

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