Is DYNAP p.Trp83Arg (c.247T>C) pathogenic?

DYNAP p.Trp83Arg (c.247T>C) is classified Uncertain significance in DYNAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: ambiguous (0.3509); Absent from gnomAD v4.1.

How common is DYNAP p.Trp83Arg (c.247T>C) in the general population?

DYNAP p.Trp83Arg (c.247T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNAP p.Trp83Arg (c.247T>C)?

AlphaMissense predicts ambiguous (score 0.3509) — an in-silico prediction, not a clinical call.

DYNAP p.Trp83Arg

c.247T>C · VCV3506010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3509 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3509	ambiguous · top 8% in DYNAP
REVEL	0.182	moderately benign-leaning
SaProt	LLR -4.98	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP 0.32
Regional constraint	o/e 1.14	unconstrained · MANE · 6,859 bp · p 0.034 · regional, not allelic
Overall
CADD	19.27	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM W109R vs ClinVar W83R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYNAP
Protein: p.Trp83Arg
Coding: c.247T>C
MANE Select: NM_173629
Type: single nucleotide variant
Location: chr18:54597837 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 60.24

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

Similar variants

DYNAP c.13A>C Uncertain significance ★ ⚠ same type
DYNAP c.14T>C Uncertain significance ★ same type
DYNAP c.20G>A Uncertain significance ★ ⚠ same type
DYNAP c.28C>A Uncertain significance ★ ⚠ same type
DYNAP c.-29G>C Uncertain significance ★ ⚠ same type
DYNAP p.Ala158Asp Uncertain significance ★ ⚠ same type
DYNAP p.Ala169Thr Uncertain significance ★ ⚠ same type
DYNAP p.Ala29Pro 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/dynap-p-trp83arg (accessed [today's date]).

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