Is PTDSS1 p.Ser283Phe (c.848C>T) pathogenic?

PTDSS1 p.Ser283Phe (c.848C>T) is classified Likely pathogenic in PTDSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-02). AlphaMissense: likely pathogenic (0.8646); Absent from gnomAD v4.1; Associated with Lenz-Majewski hyperostotic dwarfism.

What condition is associated with PTDSS1 p.Ser283Phe (c.848C>T)?

PTDSS1 p.Ser283Phe (c.848C>T) is associated with Lenz-Majewski hyperostotic dwarfism (ClinVar).

How common is PTDSS1 p.Ser283Phe (c.848C>T) in the general population?

PTDSS1 p.Ser283Phe (c.848C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTDSS1 p.Ser283Phe (c.848C>T)?

AlphaMissense predicts likely pathogenic (score 0.8646) — an in-silico prediction, not a clinical call.

PTDSS1 p.Ser283Phe

c.848C>T · rs1811091915 · VCV1027889

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8646 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Lenz-Majewski hyperostotic dwarfism

Computational evidence

Protein change
AlphaMissense	0.8646	likely pathogenic ✓ concordant with ClinVar
REVEL	0.654	pathogenic-leaning
SaProt	LLR -15.21	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 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 58 kb · p 3e-14 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

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: PTDSS1
Protein: p.Ser283Phe
Coding: c.848C>T
MANE Select: NM_014754
dbSNP: rs1811091915
Type: single nucleotide variant
Location: chr8:96304135 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.33 · 6 PDB

Full PTDSS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Lenz-Majewski hyperostotic dwarfism — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTDSS1 p.Arg95Gln Pathogenic/Likely pathogenic ★★ same condition
PTDSS1 p.Gly229Asp Uncertain significance ★★ ⚠ same condition
PTDSS1 p.Lys434Thr Uncertain significance ★★ ⚠ same condition
PTDSS1 p.Pro92Leu Uncertain significance ★★ ⚠ same condition
PTDSS1 c.1073+48T>A Benign ★★ same condition
PTDSS1 c.1242+27A>G Benign ★★ same condition
PTDSS1 p.Gln353Arg Pathogenic ★ same condition
PTDSS1 p.Asn468Lys 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/ptdss1-p-ser283phe (accessed [today's date]).

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