Is DPYSL5 p.Pro122Arg (c.365C>G) pathogenic?

DPYSL5 p.Pro122Arg (c.365C>G) is classified Uncertain significance in DPYSL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.1461); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DPYSL5 p.Pro122Arg (c.365C>G)?

DPYSL5 p.Pro122Arg (c.365C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DPYSL5 p.Pro122Arg (c.365C>G) in the general population?

DPYSL5 p.Pro122Arg (c.365C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DPYSL5 p.Pro122Arg (c.365C>G)?

AlphaMissense predicts likely benign (score 0.1461) — an in-silico prediction, not a clinical call.

DPYSL5 p.Pro122Arg

c.365C>G · VCV3273722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1461	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -9.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 44 kb · p 1e-21 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Overall 0.000657% 1/152,210 alleles · very rare

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: DPYSL5
Protein: p.Pro122Arg
Coding: c.365C>G
MANE Select: NM_020134
Type: single nucleotide variant
Location: chr2:26924990 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.21 · 3 PDB
Residue 122: a turn

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.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.Arg231Cys 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-pro122arg (accessed [today's date]).

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