Is DSPP p.Phe93Leu (c.279T>G) pathogenic?

DSPP p.Phe93Leu (c.279T>G) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely pathogenic (0.5703); Very rare (popmax 0.00329%, sas).

How common is DSPP p.Phe93Leu (c.279T>G) in the general population?

DSPP p.Phe93Leu (c.279T>G) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about DSPP p.Phe93Leu (c.279T>G)?

AlphaMissense predicts likely pathogenic (score 0.5703) — an in-silico prediction, not a clinical call.

DSPP p.Phe93Leu

c.279T>G · rs763608560 · VCV1378095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5703	likely pathogenic
REVEL	0.117	moderately benign-leaning
SaProt	LLR -4.79	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.57	GERP -2
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	4.09	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

Grpmax group 0.00329% South Asian · 3/91,048 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000616% 9/1,461,688 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,349
European (non-Finnish)	0.000509%	196,651

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: DSPP
Protein: p.Phe93Leu
Coding: c.279T>G
dbSNP: rs763608560
Type: single nucleotide variant
Location: chr4:87612465 (GRCh38)

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

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-phe93leu (accessed [today's date]).

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