Is DSPP p.Ser83Phe (c.248C>T) pathogenic?

DSPP p.Ser83Phe (c.248C>T) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1955); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser83Phe (c.248C>T)?

DSPP p.Ser83Phe (c.248C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser83Phe (c.248C>T) in the general population?

DSPP p.Ser83Phe (c.248C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSPP p.Ser83Phe (c.248C>T)?

AlphaMissense predicts likely benign (score 0.1955) — an in-silico prediction, not a clinical call.

DSPP p.Ser83Phe

c.248C>T · VCV4245170

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1955 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1955	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.85	GERP 0.99, phastCons 0.001
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	19.92	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: DSPP
Protein: p.Ser83Phe
Coding: c.248C>T
MANE Select: NM_014208
Type: single nucleotide variant
Location: chr4:87612434 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/dspp-p-ser83phe (accessed [today's date]).

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