Is PDSS1 p.Ser155Phe (c.464C>T) pathogenic?

PDSS1 p.Ser155Phe (c.464C>T) is classified Uncertain significance in PDSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). AlphaMissense: likely benign (0.1687); Absent from gnomAD v4.1; Associated with deafness-encephaloneuropathy-obesity-valvulopathy syndrome.

What condition is associated with PDSS1 p.Ser155Phe (c.464C>T)?

PDSS1 p.Ser155Phe (c.464C>T) is associated with deafness-encephaloneuropathy-obesity-valvulopathy syndrome (ClinVar).

How common is PDSS1 p.Ser155Phe (c.464C>T) in the general population?

PDSS1 p.Ser155Phe (c.464C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDSS1 p.Ser155Phe (c.464C>T)?

AlphaMissense predicts likely benign (score 0.1687) — an in-silico prediction, not a clinical call.

PDSS1 p.Ser155Phe

Q: How is Deafness-encephaloneuropathy-obesity-valvulopathy syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.464C>T · VCV3594273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

deafness-encephaloneuropathy-obesity-valvulopathy syndrome

Computational evidence

Protein change
AlphaMissense	0.1687	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 41 kb · p 6.7e-08 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: PDSS1
Protein: p.Ser155Phe
Coding: c.464C>T
MANE Select: NM_014317
Type: single nucleotide variant
Location: chr10:26709765 (GRCh38)
Gene constraint: LOEUF 1.163 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.45

Full PDSS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

deafness-encephaloneuropathy-obesity-valvulopathy syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Deafness-encephaloneuropathy-obesity-valvulopathy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PDSS1 p.Arg221Ter Likely pathogenic ★★ same condition
PDSS1 p.Trp6Ter Likely pathogenic ★★ same condition
PDSS1 c.129+5G>C Uncertain significance ★★ same condition
PDSS1 p.Ala268Thr Uncertain significance ★★ ⚠ same condition
PDSS1 p.Ala380Thr Uncertain significance ★★ ⚠ same condition
PDSS1 p.Arg146Gln Uncertain significance ★★ ⚠ same condition
PDSS1 p.Arg163His Uncertain significance ★★ ⚠ same condition
PDSS1 p.Arg240His 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/pdss1-p-ser155phe (accessed [today's date]).

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