Is PSPH p.Asp42= (c.126C>T) pathogenic?

PSPH p.Asp42= (c.126C>T) is classified Benign/Likely benign in PSPH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-27). Common (popmax 10.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with PSPH deficiency.

What condition is associated with PSPH p.Asp42= (c.126C>T)?

PSPH p.Asp42= (c.126C>T) is associated with PSPH deficiency (ClinVar).

PSPH p.Asp42=

Q: How common is PSPH p.Asp42= (c.126C>T) in the general population?

PSPH p.Asp42= (c.126C>T) is common (popmax 10.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.126C>T · rs75497420 · VCV908537

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 10.7%, eas) — too common for a highly-penetrant pathogenic allele

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 -2.1	GERP -1.9
Overall
CADD	2.458	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.7% East Asian · 2,782/25,944 alleles

Filtering AF 10.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.3%

Overall 1.27% 17,640/1,393,046 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	10.7%	9
African / African-American	5.57%	18
Admixed American	4.89%	20
South Asian	3.92%	26
Finnishnot grpmax-eligible	3.47%	29
Middle Eastern	1.78%	56
Remaining individualsnot grpmax-eligible	1.27%	79
Ashkenazi Jewishnot grpmax-eligible	0.863%	116
Amishnot grpmax-eligible	0.728%	137
European (non-Finnish)	0.413%	242

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.Asp42=
Coding: c.126C>T
MANE Select: NM_004577
dbSNP: rs75497420
Type: single nucleotide variant
Location: chr7:56021087 (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 42: 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.Asp42Val 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-asp42 (accessed [today's date]).

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