Is SRD5A3 p.Pro103Ser (c.307C>T) pathogenic?

SRD5A3 p.Pro103Ser (c.307C>T) is classified Uncertain significance in SRD5A3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-05-30). AlphaMissense: likely benign (0.0755); Ultra-rare (popmax 0.0242%, sas); Associated with Inborn genetic diseases.

What condition is associated with SRD5A3 p.Pro103Ser (c.307C>T)?

SRD5A3 p.Pro103Ser (c.307C>T) is associated with Inborn genetic diseases, isolated cerebellar hypoplasia/agenesis, SRD5A3-congenital disorder of glycosylation (ClinVar).

How common is SRD5A3 p.Pro103Ser (c.307C>T) in the general population?

SRD5A3 p.Pro103Ser (c.307C>T) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about SRD5A3 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.0755) — an in-silico prediction, not a clinical call.

SRD5A3 p.Pro103Ser

c.307C>T · rs767876488 · VCV2356101

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0755 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0755	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -8.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.59, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 13 kb · p 0.42 · regional, not allelic
Overall
CADD	17.78	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; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0242% South Asian · 22/91,048 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00143% 23/1,613,806 alleles · ultra-rare exomes 22/1,461,890 · genomes 1/151,916 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,139
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Pro103Ser
Coding: c.307C>T
MANE Select: NM_024592
dbSNP: rs767876488
Type: single nucleotide variant
Location: chr4:55359431 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.07
Residue 103: a UniProt-annotated variant site (in cdg1q)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: isolated cerebellar hypoplasia/agenesis SRD5A3-congenital disorder of glycosylation

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-pro103ser (accessed [today's date]).

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