Is PSPH p.Ala43= (c.129G>A) pathogenic?

PSPH p.Ala43= (c.129G>A) is classified Conflicting classifications of pathogenicity in PSPH (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-13). Ultra-rare (popmax 0.0454%, afr); Associated with PSPH deficiency.

What condition is associated with PSPH p.Ala43= (c.129G>A)?

PSPH p.Ala43= (c.129G>A) is associated with PSPH deficiency (ClinVar).

How common is PSPH p.Ala43= (c.129G>A) in the general population?

PSPH p.Ala43= (c.129G>A) is ultra-rare (popmax 0.0454%, afr) (gnomAD).

PSPH p.Ala43=

c.129G>A · rs548513131 · VCV360511

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0454%, afr)

Conditions

PSPH deficiency

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 -9.4
Overall
CADD	1.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0454% African / African-American · 34/74,814 alleles

Filtering AF 0.0334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0292%

Overall 0.00521% 84/1,613,790 alleles · ultra-rare exomes 63/1,461,790 · genomes 21/152,000 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0454%	2,200
Admixed American	0.0167%	5,997
Middle Eastern	0.0165%	6,062
South Asian	0.00879%	11,383
Remaining individualsnot grpmax-eligible	0.0064%	15,621
East Asian	0.00223%	44,854
European (non-Finnish)	0.00212%	47,200
Finnishnot grpmax-eligible	0.00156%	64,024

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.Ala43=
Coding: c.129G>A
MANE Select: NM_004577
dbSNP: rs548513131
Type: single nucleotide variant
Location: chr7:56021084 (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 43: a turn

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.Ala43Val Uncertain significance ★ ⚠ 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.Asp32Asn 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-ala43 (accessed [today's date]).

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