Is PSPH p.Asp32Asn (c.94G>A) pathogenic?

PSPH p.Asp32Asn (c.94G>A) is classified Uncertain significance in PSPH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.8379); Rare (popmax 0.103%, afr); Associated with PSPH deficiency.

What condition is associated with PSPH p.Asp32Asn (c.94G>A)?

PSPH p.Asp32Asn (c.94G>A) is associated with PSPH deficiency (ClinVar).

How common is PSPH p.Asp32Asn (c.94G>A) in the general population?

PSPH p.Asp32Asn (c.94G>A) is rare (popmax 0.103%, afr) (gnomAD).

What do computational predictors say about PSPH p.Asp32Asn (c.94G>A)?

AlphaMissense predicts likely pathogenic (score 0.8379) — an in-silico prediction, not a clinical call.

PSPH p.Asp32Asn

c.94G>A · rs104894035 · VCV13623

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8379 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PSPH deficiency

Computational evidence

Protein change
AlphaMissense	0.8379	likely pathogenic
REVEL	0.661	pathogenic-leaning
SaProt	LLR -12.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 4.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 9,447 bp · p 0.0022 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.103% African / African-American · 77/74,412 alleles

Filtering AF 0.0848% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.078%

Overall 0.00663% 107/1,613,480 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.103%	966
Admixed American	0.0183%	5,454
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00127%	78,667
South Asian	0.0011%	91,080

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: PSPH
Protein: p.Asp32Asn
Coding: c.94G>A
MANE Select: NM_004577
dbSNP: rs104894035
Type: single nucleotide variant
Location: chr7:56021119 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 6 PDB
Residue 32: a UniProt-annotated variant site (in psphd; decreased l-phosphoserine phosphatase activity); an α-helix

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

Disease context

PSPH deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PSPH p.Asp32Gly Benign/Likely benign ★★ same residue
PSPH p.Arg101Ter Likely pathogenic ★★ same condition
PSPH c.422-3A>C Uncertain significance ★★ same condition
PSPH c.570+3A>G Uncertain significance ★★ same condition
PSPH c.570+5G>C Uncertain significance ★★ same condition
PSPH c.*341G>A Uncertain significance ★★ same condition
PSPH p.Asn124Ser Uncertain significance ★★ ⚠ same condition
PSPH p.Gln204His 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/psph-p-asp32asn (accessed [today's date]).

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