Is DSPP p.Val420Ala (c.1259T>C) pathogenic?

DSPP p.Val420Ala (c.1259T>C) is classified Benign/Likely benign in DSPP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0944); Rare (popmax 0.393%, nfe).

How common is DSPP p.Val420Ala (c.1259T>C) in the general population?

DSPP p.Val420Ala (c.1259T>C) is rare (popmax 0.393%, nfe) (gnomAD).

What do computational predictors say about DSPP p.Val420Ala (c.1259T>C)?

AlphaMissense predicts likely benign (score 0.0944) — an in-silico prediction, not a clinical call.

DSPP p.Val420Ala

c.1259T>C · rs191967636 · VCV995083

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0944 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.393%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0944	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -8.4	GERP -2.6
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	0.009	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 0.393% European (non-Finnish) · 4,634/1,179,984 alleles

Filtering AF 0.383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.379%

Overall 0.479% 7,733/1,613,832 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	4.06%	25
European (non-Finnish)grpmax	0.393%	255
Remaining individualsnot grpmax-eligible	0.392%	255
South Asian	0.205%	487
Admixed American	0.0583%	1,714
African / African-American	0.0454%	2,202
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val420Ala
Coding: c.1259T>C
dbSNP: rs191967636
Type: single nucleotide variant
Location: chr4:87613921 (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-val420ala (accessed [today's date]).

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