Is PSMA2 p.Pro144Ser (c.430C>T) pathogenic?

PSMA2 p.Pro144Ser (c.430C>T) is classified Uncertain significance in PSMA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely pathogenic (0.677); Absent from gnomAD v4.1.

How common is PSMA2 p.Pro144Ser (c.430C>T) in the general population?

PSMA2 p.Pro144Ser (c.430C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PSMA2 p.Pro144Ser (c.430C>T)?

AlphaMissense predicts likely pathogenic (score 0.677) — an in-silico prediction, not a clinical call.

PSMA2 p.Pro144Ser

c.430C>T · VCV3939583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.677 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.677	likely pathogenic
REVEL	0.613	indeterminate
SaProt	LLR -10.93	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.14	constrained · MANE · 1,502 bp · p 9.9e-09 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PSMA2
Protein: p.Pro144Ser
Coding: c.430C>T
MANE Select: NM_002787
Type: single nucleotide variant
Location: chr7:42923351 (GRCh38)
Gene constraint: LOEUF 0.243 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.74 · 177 PDB
Residue 144: a β-strand

Full PSMA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSMA2 p.Ala2Thr Uncertain significance ★ ⚠ same type
PSMA2 p.Asp58Glu Uncertain significance ★ ⚠ same type
PSMA2 p.Gln96Arg Uncertain significance ★ ⚠ same type
PSMA2 p.Glu215Gly Uncertain significance ★ ⚠ same type
PSMA2 p.Ser9Trp Uncertain significance ★ ⚠ same type
PSMA2 p.Pro129= Benign ★ same type

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/psma2-p-pro144ser (accessed [today's date]).

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