Is SIX5 p.Arg150= (c.450C>T) pathogenic?

SIX5 p.Arg150= (c.450C>T) is classified Likely benign in SIX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). Very rare (popmax 0.00114%, sas).

How common is SIX5 p.Arg150= (c.450C>T) in the general population?

SIX5 p.Arg150= (c.450C>T) is very rare (popmax 0.00114%, sas) (gnomAD).

SIX5 p.Arg150=

c.450C>T · VCV3684921

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.1	GERP -0.64, phastCons 1
Overall
CADD	12.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00114% South Asian · 1/87,890 alleles

Overall 0.000127% 2/1,572,402 alleles · very rare exomes 2/1,420,098 · genomes 0/152,304 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00114%	87,890
European (non-Finnish)	8.58e-05%	1,165,600

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: SIX5
Protein: p.Arg150=
Coding: c.450C>T
MANE Select: NM_175875
Type: single nucleotide variant
Location: chr19:45768395 (GRCh38)

Full SIX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/six5-p-arg150 (accessed [today's date]).

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