Is DPT p.Trp102Arg (c.304T>A) pathogenic?

DPT p.Trp102Arg (c.304T>A) is classified Uncertain significance in DPT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-04). AlphaMissense: likely pathogenic (0.9963); Very rare (popmax 0.00534%, afr).

How common is DPT p.Trp102Arg (c.304T>A) in the general population?

DPT p.Trp102Arg (c.304T>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about DPT p.Trp102Arg (c.304T>A)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

DPT p.Trp102Arg

c.304T>A · VCV4244590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic · top 4% in DPT
REVEL	0.497	indeterminate
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 33 kb · p 0.84 · regional, not allelic
Overall
CADD	29.0	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 0.00534% African / African-American · 4/74,916 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,856 alleles · very rare exomes 1/1,461,728 · genomes 3/152,128 · 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: DPT
Protein: p.Trp102Arg
Coding: c.304T>A
MANE Select: NM_001937
Type: single nucleotide variant
Location: chr1:168728871 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.21
Residue 102: the '2 x 53-55 aa tandem repeats' region; the '3 x 6 aa repeats of d-r-[eq]-w-[nqk]-[fy]' region

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

Similar variants

DPT p.Ala58= Benign ★★ same type
DPT p.Phe130= Likely benign ★★ same type
DPT p.Ser83Ile Likely benign ★★ same type
DPT p.Tyr194= Benign ★★ same type
DPT p.Val201Ile Benign ★★ same type
DPT p.Arg126Gln Uncertain significance ★ ⚠ same type
DPT p.Arg134Cys Uncertain significance ★ ⚠ same type
DPT p.Arg134His Uncertain significance ★ ⚠ 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/dpt-p-trp102arg (accessed [today's date]).

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