Is PSPH p.Arg101Ter (c.301C>T) pathogenic?

PSPH p.Arg101Ter (c.301C>T) is classified Likely pathogenic in PSPH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-21). Very rare (popmax 0.000681%, nfe); Associated with PSPH deficiency.

What condition is associated with PSPH p.Arg101Ter (c.301C>T)?

PSPH p.Arg101Ter (c.301C>T) is associated with PSPH deficiency (ClinVar).

How common is PSPH p.Arg101Ter (c.301C>T) in the general population?

PSPH p.Arg101Ter (c.301C>T) is very rare (popmax 0.000681%, nfe) (gnomAD).

PSPH p.Arg101Ter

c.301C>T · rs1264747554 · VCV978149

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000681%, nfe)

Conditions

PSPH deficiency

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 6 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 2.8, phastCons 1
Overall
CADD	38.0	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 0.000681% European (non-Finnish) · 8/1,175,304 alleles

Filtering AF 0.000293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000212%

Overall 0.000561% 9/1,604,180 alleles · very rare exomes 9/1,454,572 · genomes 0/149,608 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	61,950
European (non-Finnish)grpmax	0.000681%	146,913

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg101Ter
Coding: c.301C>T
MANE Select: NM_004577
dbSNP: rs1264747554
Type: single nucleotide variant
Location: chr7:56017354 (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.Arg101Gln Uncertain significance ★ ⚠ same residue
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-arg101ter (accessed [today's date]).

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