Is SETD5 p.Pro192Ser (c.574C>T) pathogenic?

SETD5 p.Pro192Ser (c.574C>T) is classified Uncertain significance in SETD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-23). AlphaMissense: likely benign (0.1143); Absent from gnomAD v4.1.

How common is SETD5 p.Pro192Ser (c.574C>T) in the general population?

SETD5 p.Pro192Ser (c.574C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SETD5 p.Pro192Ser (c.574C>T)?

AlphaMissense predicts likely benign (score 0.1143) — an in-silico prediction, not a clinical call.

SETD5 p.Pro192Ser

c.574C>T · rs536577273 · VCV1810427

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1143 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1143	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -5.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 12 kb · p 2.7e-05 · regional, not allelic
Overall
CADD	25.6	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: SETD5
Protein: p.Pro192Ser
Coding: c.574C>T
MANE Select: NM_001080517
dbSNP: rs536577273
Type: single nucleotide variant
Location: chr3:9440462 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 192: the 'disordered' region

Full SETD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETD5 p.Pro192= Likely benign ★ same residue
SETD5 c.1441-1G>A Pathogenic ★★ same type
SETD5 c.1525-1G>C Pathogenic/Likely pathogenic ★★ same type
SETD5 c.2347-1G>A Pathogenic ★★ same type
SETD5 c.2347-7A>G Pathogenic ★★ same type
SETD5 c.3631+1G>A Pathogenic ★★ same type
SETD5 c.960-5C>G Pathogenic/Likely pathogenic ★★ same type
SETD5 p.Arg1001Ter Pathogenic ★★ 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/setd5-p-pro192ser (accessed [today's date]).

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