Is DPYSL5 p.Arg231Cys (c.691C>T) pathogenic?

DPYSL5 p.Arg231Cys (c.691C>T) is classified Uncertain significance in DPYSL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.9704); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DPYSL5 p.Arg231Cys (c.691C>T)?

DPYSL5 p.Arg231Cys (c.691C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DPYSL5 p.Arg231Cys (c.691C>T) in the general population?

DPYSL5 p.Arg231Cys (c.691C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPYSL5 p.Arg231Cys (c.691C>T)?

AlphaMissense predicts likely pathogenic (score 0.9704) — an in-silico prediction, not a clinical call.

DPYSL5 p.Arg231Cys

c.691C>T · rs2465501914 · VCV3085688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9704 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9704	likely pathogenic
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -15.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.92, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 44 kb · p 1e-21 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

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: DPYSL5
Protein: p.Arg231Cys
Coding: c.691C>T
MANE Select: NM_020134
dbSNP: rs2465501914
Type: single nucleotide variant
Location: chr2:26931661 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.21 · 3 PDB
Residue 231: an α-helix

Full DPYSL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPYSL5 p.Arg231His Uncertain significance ★ ⚠ same residue
DPYSL5 p.Ala375Thr Uncertain significance ★★ ⚠ same condition
DPYSL5 p.Lys123Arg Uncertain significance ★★ ⚠ same condition
DPYSL5 p.Val132Met Uncertain significance ★★ ⚠ same condition
DPYSL5 p.Ala129Thr Uncertain significance ★ ⚠ same condition
DPYSL5 p.Arg372Cys Uncertain significance ★ ⚠ same condition
DPYSL5 p.Arg442Trp Uncertain significance ★ ⚠ same condition
DPYSL5 p.Asn237Lys Uncertain significance ★ ⚠ same condition

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/dpysl5-p-arg231cys (accessed [today's date]).

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