Is PATL2 p.Pro173Ser (c.517C>T) pathogenic?

PATL2 p.Pro173Ser (c.517C>T) is classified Uncertain significance in PATL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.0704); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PATL2 p.Pro173Ser (c.517C>T)?

PATL2 p.Pro173Ser (c.517C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PATL2 p.Pro173Ser (c.517C>T) in the general population?

PATL2 p.Pro173Ser (c.517C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PATL2 p.Pro173Ser (c.517C>T)?

AlphaMissense predicts likely benign (score 0.0704) — an in-silico prediction, not a clinical call.

PATL2 p.Pro173Ser

c.517C>T · VCV3928225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0704 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0704	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -0.35, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.14 · regional, not allelic
Overall
CADD	7.501	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

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: PATL2
Protein: p.Pro173Ser
Coding: c.517C>T
MANE Select: NM_001387263
Type: single nucleotide variant
Location: chr15:44672155 (GRCh38)
Gene constraint: LOEUF 1.163 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.05
Residue 173: the 'disordered' region; a UniProt-annotated variant site (in ozema4)

Full PATL2 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

PATL2 p.Arg279His Uncertain significance ★★ ⚠ same condition
PATL2 p.Arg402Gln Uncertain significance ★★ ⚠ same condition
PATL2 p.Ala175Val Uncertain significance ★ ⚠ same condition
PATL2 p.Ala271Thr Uncertain significance ★ ⚠ same condition
PATL2 p.Ala296Ser Uncertain significance ★ ⚠ same condition
PATL2 p.Ala392Thr Uncertain significance ★ ⚠ same condition
PATL2 p.Ala76Asp Uncertain significance ★ ⚠ same condition
PATL2 p.Arg128Trp 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/patl2-p-pro173ser (accessed [today's date]).

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