Is DPYSL3 p.Pro166Ser (c.496C>T) pathogenic?

DPYSL3 p.Pro166Ser (c.496C>T) is classified Uncertain significance in DPYSL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely pathogenic (0.9593); Absent from gnomAD v4.1.

How common is DPYSL3 p.Pro166Ser (c.496C>T) in the general population?

DPYSL3 p.Pro166Ser (c.496C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPYSL3 p.Pro166Ser (c.496C>T)?

AlphaMissense predicts likely pathogenic (score 0.9593) — an in-silico prediction, not a clinical call.

DPYSL3 p.Pro166Ser

c.496C>T · VCV3842374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9593 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,936)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9593	likely pathogenic
REVEL	0.47	indeterminate
SaProt	LLR -15.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 116 kb · p 3.9e-09 · regional, not allelic
Overall
CADD	30.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P52S vs ClinVar P166S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,589,936). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DPYSL3
Protein: p.Pro166Ser
Coding: c.496C>T
MANE Select: NM_001197294
Type: single nucleotide variant
Location: chr5:147418606 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 4 PDB
Residue 166: a β-strand

Full DPYSL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPYSL3 p.Ala147Val Uncertain significance ★ ⚠ same type
DPYSL3 p.Ala174Thr Uncertain significance ★ ⚠ same type
DPYSL3 p.Ala210Thr Uncertain significance ★ ⚠ same type
DPYSL3 p.Ala530Thr Uncertain significance ★ ⚠ same type
DPYSL3 p.Ala630Thr Uncertain significance ★ ⚠ same type
DPYSL3 p.Arg475Trp Uncertain significance ★ same type
DPYSL3 p.Arg581His Uncertain significance ★ ⚠ same type
DPYSL3 p.Arg634Trp 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/dpysl3-p-pro166ser (accessed [today's date]).

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