Is DSPP p.Val18Phe (c.52G>T) pathogenic?

DSPP p.Val18Phe (c.52G>T) is classified Pathogenic in DSPP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-07). AlphaMissense: likely benign (0.216); Very rare (popmax 0.0011%, sas); Associated with DSPP-related disorders.

What condition is associated with DSPP p.Val18Phe (c.52G>T)?

DSPP p.Val18Phe (c.52G>T) is associated with DSPP-related disorders, dentinogenesis imperfecta type 2, dentinogenesis imperfecta type 3 (ClinVar).

How common is DSPP p.Val18Phe (c.52G>T) in the general population?

DSPP p.Val18Phe (c.52G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DSPP p.Val18Phe (c.52G>T)?

AlphaMissense predicts likely benign (score 0.216) — an in-silico prediction, not a clinical call.

DSPP p.Val18Phe

c.52G>T · rs121912987 · VCV16856

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.216 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DSPP-related disorders

⚠ 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	0.216	likely benign ⚠ discordant with ClinVar
REVEL	0.623	indeterminate
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.53	loss · gain 0.01 · independent
Constraint at this position
Conservation	phyloP 1.4	GERP -1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	21.1	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 0.0011% South Asian · 1/91,052 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,584 alleles · very rare exomes 3/1,461,492 · genomes 0/152,092 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,052
European (non-Finnish)	0.00017%	589,890

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.Val18Phe
Coding: c.52G>T
MANE Select: NM_014208
dbSNP: rs121912987
Type: single nucleotide variant
Location: chr4:87612105 (GRCh38)

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

Disease context

DSPP-related disorders

Also linked: dentinogenesis imperfecta type 2 dentinogenesis imperfecta type 3

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-val18phe (accessed [today's date]).

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