Is UPK3A p.Phe30= (c.90C>T) pathogenic?

UPK3A p.Phe30= (c.90C>T) is classified Benign/Likely benign in UPK3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.7%, eas); Associated with renal hypodysplasia/aplasia 1.

What condition is associated with UPK3A p.Phe30= (c.90C>T)?

UPK3A p.Phe30= (c.90C>T) is associated with renal hypodysplasia/aplasia 1 (ClinVar).

How common is UPK3A p.Phe30= (c.90C>T) in the general population?

UPK3A p.Phe30= (c.90C>T) is rare (popmax 0.7%, eas) (gnomAD).

UPK3A p.Phe30=

c.90C>T · rs199656309 · VCV341969

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.7%, eas)

Conditions

renal hypodysplasia/aplasia 1

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 -5.3	GERP -2.6
Overall
CADD	2.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.7% East Asian · 314/44,886 alleles

Filtering AF 0.636% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.611%

Overall 0.021% 339/1,614,092 alleles · rare exomes 302/1,461,844 · genomes 37/152,248 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.7%	143
Remaining individualsnot grpmax-eligible	0.024%	4,167
Admixed American	0.00333%	30,009
South Asian	0.0022%	45,541
European (non-Finnish)	0.000508%	196,664

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: UPK3A
Protein: p.Phe30=
Coding: c.90C>T
MANE Select: NM_006953
dbSNP: rs199656309
Type: single nucleotide variant
Location: chr22:45285978 (GRCh38)
Gene constraint: LOEUF 1.574 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.77

Full UPK3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

renal hypodysplasia/aplasia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UPK3A p.Arg187His Uncertain significance ★★ ⚠ same condition
UPK3A p.Asp68Asn Uncertain significance ★★ ⚠ same condition
UPK3A p.Ser111Asn Uncertain significance ★★ ⚠ same condition
UPK3A p.Ser157Leu Uncertain significance ★★ ⚠ same condition
UPK3A c.571+1G>A Benign/Likely benign ★★ same condition
UPK3A c.704+8C>G Likely benign ★★ same condition
UPK3A p.Ala154Pro Benign ★★ ⚠ same condition
UPK3A p.Gln286= Benign ★★ 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/upk3a-p-phe30 (accessed [today's date]).

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