Is SETD5 p.Ser570= (c.1710T>C) pathogenic?

SETD5 p.Ser570= (c.1710T>C) is classified Likely benign in SETD5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-29). Very rare (popmax 0.00333%, amr).

How common is SETD5 p.Ser570= (c.1710T>C) in the general population?

SETD5 p.Ser570= (c.1710T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

SETD5 p.Ser570=

c.1710T>C · rs769555032 · VCV761066

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.065	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -4
Overall
CADD	7.617	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,613,930 alleles · very rare exomes 6/1,461,704 · genomes 3/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0032%	31,231
European (non-Finnish)	0.000424%	235,981

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: SETD5
Protein: p.Ser570=
Coding: c.1710T>C
MANE Select: NM_001080517
dbSNP: rs769555032
Type: single nucleotide variant
Location: chr3:9447235 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10
Residue 570: the 'disordered' region; a UniProt-annotated variant site (in mrd23)

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

Similar variants

SETD5 p.Ser570Ala Uncertain significance ★ ⚠ same residue
SETD5 p.Ser570Cys Uncertain significance ★ ⚠ same residue
SETD5 p.Ser570fs Likely pathogenic ★ 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

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-ser570 (accessed [today's date]).

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