Is SRD5A3 p.Pro36= (c.108G>T) pathogenic?

SRD5A3 p.Pro36= (c.108G>T) is classified Conflicting classifications of pathogenicity in SRD5A3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-16). Rare (popmax 0.549%, eas); Associated with SRD5A3-congenital disorder of glycosylation.

What condition is associated with SRD5A3 p.Pro36= (c.108G>T)?

SRD5A3 p.Pro36= (c.108G>T) is associated with SRD5A3-congenital disorder of glycosylation (ClinVar).

How common is SRD5A3 p.Pro36= (c.108G>T) in the general population?

SRD5A3 p.Pro36= (c.108G>T) is rare (popmax 0.549%, eas) (gnomAD).

How is SRD5A3-CDG inherited?

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

SRD5A3 p.Pro36=

c.108G>T · rs200253126 · VCV703104

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.549%, eas)

Conditions

SRD5A3-congenital disorder of glycosylation

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 -0.68, phastCons 0.75
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.549% East Asian · 243/44,272 alleles

Filtering AF 0.492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.47%

Overall 0.0177% 284/1,606,030 alleles · rare exomes 249/1,453,804 · genomes 35/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.549%	182
Remaining individualsnot grpmax-eligible	0.0257%	3,886
South Asian	0.02%	5,006
European (non-Finnish)	0.000595%	168,151

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: SRD5A3
Protein: p.Pro36=
Coding: c.108G>T
MANE Select: NM_024592
dbSNP: rs200253126
Type: single nucleotide variant
Location: chr4:55346444 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.07
Residue 36: a UniProt-annotated variant site (in cdg1q)

Full SRD5A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SRD5A3-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For SRD5A3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SRD5A3 p.Gln162Ter Pathogenic/Likely pathogenic ★★ same condition
SRD5A3 p.Trp107Ter Pathogenic ★★ same condition
SRD5A3 p.Trp19Ter Pathogenic ★★ same condition
SRD5A3 c.*2430C>T Uncertain significance ★★ same condition
SRD5A3 c.*2641G>A Uncertain significance ★★ same condition
SRD5A3 c.*991C>T Uncertain significance ★★ same condition
SRD5A3 p.Ala17Val Uncertain significance ★★ ⚠ same condition
SRD5A3 p.Asn155Ser Uncertain significance ★★ ⚠ 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/srd5a3-p-pro36 (accessed [today's date]).

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