Is PSPH p.Val40= (c.120T>A) pathogenic?

PSPH p.Val40= (c.120T>A) is classified Benign in PSPH (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-27). Common (popmax 40.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with PSPH deficiency.

What condition is associated with PSPH p.Val40= (c.120T>A)?

PSPH p.Val40= (c.120T>A) is associated with PSPH deficiency (ClinVar).

PSPH p.Val40=

Q: How common is PSPH p.Val40= (c.120T>A) in the general population?

PSPH p.Val40= (c.120T>A) is common (popmax 40.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.120T>A · rs202027697 · VCV360512

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 40.4%, afr) — 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 -0.19	GERP -3.2
Overall
CADD	0.933	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 40.4% African / African-American · 16,565/40,994 alleles

Filtering AF 39.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.7%

Overall 5.02% 60,051/1,195,666 alleles · common exomes 42,992/1,088,914 · genomes 17,059/106,752 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	40.4%	2
East Asian	31.9%	3
Admixed American	13.3%	8
South Asian	12.4%	8
Finnishnot grpmax-eligible	9.98%	10
Middle Eastern	7.48%	13
Remaining individualsnot grpmax-eligible	5.25%	19
Ashkenazi Jewishnot grpmax-eligible	3.89%	26
European (non-Finnish)	1.82%	55
Amishnot grpmax-eligible	1.54%	65

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.Val40=
Coding: c.120T>A
MANE Select: NM_004577
dbSNP: rs202027697
Type: single nucleotide variant
Location: chr7:56021093 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 6 PDB

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.Val40Phe 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-val40 (accessed [today's date]).

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