Is SRD5A2 p.Val18= (c.54C>T) pathogenic?

SRD5A2 p.Val18= (c.54C>T) is classified Likely benign in SRD5A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). Ultra-rare (popmax 0.0331%, mid); Associated with 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency.

What condition is associated with SRD5A2 p.Val18= (c.54C>T)?

SRD5A2 p.Val18= (c.54C>T) is associated with 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency (ClinVar).

How common is SRD5A2 p.Val18= (c.54C>T) in the general population?

SRD5A2 p.Val18= (c.54C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

SRD5A2 p.Val18=

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.54C>T · rs769913545 · VCV2961684

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

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 -0.47	GERP -4.5
Overall
CADD	0.817	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,044 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.000685% 10/1,459,366 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,022
East Asian	0.00892%	11,207
Admixed American	0.00333%	29,994
Remaining individualsnot grpmax-eligible	0.0016%	62,418
African / African-American	0.00133%	75,042

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.Val18=
Coding: c.54C>T
MANE Select: NM_000348
dbSNP: rs769913545
Type: single nucleotide variant
Location: chr2:31580847 (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 18: an α-helix

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-val18 (accessed [today's date]).

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