Is UPK3A p.Pro155= (c.465C>T) pathogenic?

UPK3A p.Pro155= (c.465C>T) is classified Benign in UPK3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-12). Common (popmax 8.13%, afr) — too common for a highly-penetrant pathogenic allele; Associated with renal hypodysplasia/aplasia 1.

What condition is associated with UPK3A p.Pro155= (c.465C>T)?

UPK3A p.Pro155= (c.465C>T) is associated with renal hypodysplasia/aplasia 1 (ClinVar).

UPK3A p.Pro155=

Q: How common is UPK3A p.Pro155= (c.465C>T) in the general population?

UPK3A p.Pro155= (c.465C>T) is common (popmax 8.13%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.465C>T · rs62001037 · VCV341978

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.13%, afr) — too common for a highly-penetrant pathogenic allele

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 -2.2	GERP -2.3
Overall
CADD	1.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.13% African / African-American · 6,082/74,838 alleles

Filtering AF 7.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.89%

Overall 0.436% 6,996/1,603,372 alleles · common exomes 3,573/1,451,086 · genomes 3,423/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.13%	12
Admixed American	0.597%	168
Remaining individualsnot grpmax-eligible	0.53%	189
Middle Eastern	0.529%	189
Ashkenazi Jewishnot grpmax-eligible	0.041%	2,440
South Asian	0.0301%	3,319
European (non-Finnish)	0.0145%	6,913

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.Pro155=
Coding: c.465C>T
MANE Select: NM_006953
dbSNP: rs62001037
Type: single nucleotide variant
Location: chr22:45287428 (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.Pro155Ser Uncertain significance ★ ⚠ same residue
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

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-pro155 (accessed [today's date]).

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