Is SETD5 p.Thr203= (c.609T>G) pathogenic?

SETD5 p.Thr203= (c.609T>G) is classified Benign/Likely benign in SETD5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-26). Rare (popmax 0.103%, sas).

How common is SETD5 p.Thr203= (c.609T>G) in the general population?

SETD5 p.Thr203= (c.609T>G) is rare (popmax 0.103%, sas) (gnomAD).

SETD5 p.Thr203=

c.609T>G · rs201728851 · VCV727297

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.103%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP -3.4, phastCons 1
Overall
CADD	8.906	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% South Asian · 94/90,902 alleles

Filtering AF 0.0865% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0802%

Overall 0.0486% 780/1,606,468 alleles · rare exomes 683/1,454,142 · genomes 97/152,326 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.686%	146
South Asiangrpmax	0.103%	967
Remaining individualsnot grpmax-eligible	0.0627%	1,595
Middle Eastern	0.0497%	2,013
European (non-Finnish)	0.017%	5,895
Admixed American	0.005%	19,995
East Asian	0.00446%	22,421
African / African-American	0.00134%	74,884

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr203=
Coding: c.609T>G
MANE Select: NM_001080517
dbSNP: rs201728851
Type: single nucleotide variant
Location: chr3:9440497 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 47.10

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

Similar variants

SETD5 p.Thr203Ala Uncertain significance ★ ⚠ 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-thr203 (accessed [today's date]).

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