Is DSP p.Val505Phe (c.1513G>T) pathogenic?

DSP p.Val505Phe (c.1513G>T) is classified Likely pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2014-07-09). AlphaMissense: likely pathogenic (0.8772); Very rare (popmax 0.00134%, afr).

How common is DSP p.Val505Phe (c.1513G>T) in the general population?

DSP p.Val505Phe (c.1513G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DSP p.Val505Phe (c.1513G>T)?

AlphaMissense predicts likely pathogenic (score 0.8772) — an in-silico prediction, not a clinical call.

DSP p.Val505Phe

c.1513G>T · rs794728113 · VCV199862

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8772	likely pathogenic ✓ concordant with ClinVar
REVEL	0.524	indeterminate
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	28.4	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 0.00134% African / African-American · 1/74,904 alleles

Overall 6.2e-05% 1/1,614,038 alleles · very rare exomes 0/1,461,892 · genomes 1/152,146 · joint denominator

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: DSP
Protein: p.Val505Phe
Coding: c.1513G>T
MANE Select: NM_004415
dbSNP: rs794728113
Type: single nucleotide variant
Location: chr6:7569279 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 505: a β-strand; the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; the sh3 domain; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in arvd8; likely pathogenic; results in an unstable protein that forms perinuclear aggregates); a UniProt-annotated variant site (in arvd8 and dcwhkta; uncertain significance); a UniProt-annotated variant site (in arvd8)

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

Similar variants

DSP p.Val505Ile Uncertain significance ★★ ⚠ same residue
DSP c.1141-2A>G Likely pathogenic ★★ same type
DSP c.1141-2A>T Likely pathogenic ★★ same type
DSP c.1266+2T>C Likely pathogenic ★★ same type
DSP c.1574+1G>A Likely pathogenic ★★ same type
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same type
DSP c.2297+1G>A Likely pathogenic ★★ same type
DSP c.2298-1G>C Likely pathogenic ★★ same type

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/dsp-p-val505phe (accessed [today's date]).

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