Is PSPH p.Thr24= (c.72G>C) pathogenic?

PSPH p.Thr24= (c.72G>C) is classified Likely benign in PSPH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-01). Rare (popmax 0.372%, nfe); Associated with PSPH deficiency.

What condition is associated with PSPH p.Thr24= (c.72G>C)?

PSPH p.Thr24= (c.72G>C) is associated with PSPH deficiency (ClinVar).

How common is PSPH p.Thr24= (c.72G>C) in the general population?

PSPH p.Thr24= (c.72G>C) is rare (popmax 0.372%, nfe) (gnomAD).

PSPH p.Thr24=

c.72G>C · rs145408555 · VCV360516

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.372%, nfe)

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 -20	GERP -11
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.372% European (non-Finnish) · 4,391/1,180,008 alleles

Filtering AF 0.363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.359%

Overall 0.307% 4,953/1,614,208 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.372%	269
Finnishnot grpmax-eligible	0.336%	298
Remaining individualsnot grpmax-eligible	0.214%	466
Admixed American	0.155%	645
South Asian	0.0779%	1,283
African / African-American	0.0613%	1,632
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.Thr24=
Coding: c.72G>C
MANE Select: NM_004577
dbSNP: rs145408555
Type: single nucleotide variant
Location: chr7:56021141 (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 24: 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.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
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-thr24 (accessed [today's date]).

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