Is DSPP p.Val317Ala (c.950T>C) pathogenic?

DSPP p.Val317Ala (c.950T>C) is classified Uncertain significance in DSPP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-23). AlphaMissense: likely benign (0.0606); Ultra-rare (popmax 0.0164%, mid).

How common is DSPP p.Val317Ala (c.950T>C) in the general population?

DSPP p.Val317Ala (c.950T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DSPP p.Val317Ala (c.950T>C)?

AlphaMissense predicts likely benign (score 0.0606) — an in-silico prediction, not a clinical call.

DSPP p.Val317Ala

c.950T>C · rs770374924 · VCV2195407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0606 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0606	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7.1	GERP -2.7
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	0.001	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

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00136% 22/1,613,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00891%	11,222
African / African-American	0.00401%	24,967
South Asian	0.0022%	45,534
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,006
European (non-Finnish)	0.000847%	118,004

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.Val317Ala
Coding: c.950T>C
dbSNP: rs770374924
Type: single nucleotide variant
Location: chr4:87613136 (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-val317ala (accessed [today's date]).

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