Is PSPH p.Arg50Ter (c.148C>T) pathogenic?

PSPH p.Arg50Ter (c.148C>T) is classified Pathogenic in PSPH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-29). Very rare (popmax 0.00439%, sas).

How common is PSPH p.Arg50Ter (c.148C>T) in the general population?

PSPH p.Arg50Ter (c.148C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

PSPH p.Arg50Ter

c.148C>T · VCV4088159

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 8
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 1.6, phastCons 0.36
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,064 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000496% 8/1,613,244 alleles · very rare exomes 8/1,460,896 · genomes 0/152,348 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,766
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
East Asian	0.00223%	44,878
Remaining individualsnot grpmax-eligible	0.0016%	62,440
Finnishnot grpmax-eligible	0.00157%	63,682

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.Arg50Ter
Coding: c.148C>T
MANE Select: NM_004577
Type: single nucleotide variant
Location: chr7:56019727 (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

Similar variants

PSPH p.Arg50Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PSPH p.Arg101Ter Likely pathogenic ★★ same type
PSPH c.422-3A>C Uncertain significance ★★ same type
PSPH c.570+3A>G Uncertain significance ★★ same type
PSPH c.570+5G>C Uncertain significance ★★ same type
PSPH c.*341G>A Uncertain significance ★★ same type
PSPH p.Asn124Ser Uncertain significance ★★ ⚠ same type
PSPH p.Asp32Asn Uncertain significance ★★ ⚠ same type

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-arg50ter (accessed [today's date]).

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