Is PSPH p.Ser155Phe (c.464C>T) pathogenic?

PSPH p.Ser155Phe (c.464C>T) is classified Uncertain significance in PSPH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-15). AlphaMissense: likely pathogenic (0.7713); Absent from gnomAD v4.1; Associated with PSPH deficiency.

What condition is associated with PSPH p.Ser155Phe (c.464C>T)?

PSPH p.Ser155Phe (c.464C>T) is associated with PSPH deficiency (ClinVar).

How common is PSPH p.Ser155Phe (c.464C>T) in the general population?

PSPH p.Ser155Phe (c.464C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PSPH p.Ser155Phe (c.464C>T)?

AlphaMissense predicts likely pathogenic (score 0.7713) — an in-silico prediction, not a clinical call.

PSPH p.Ser155Phe

c.464C>T · rs2534834720 · VCV1994879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7713 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PSPH deficiency

Computational evidence

Protein change
AlphaMissense	0.7713	likely pathogenic
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -12.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 4.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 9,447 bp · p 0.0022 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PSPH
Protein: p.Ser155Phe
Coding: c.464C>T
MANE Select: NM_004577
dbSNP: rs2534834720
Type: single nucleotide variant
Location: chr7:56015129 (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.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-ser155phe (accessed [today's date]).

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