Is SIX5 p.Asp200= (c.600C>T) pathogenic?

SIX5 p.Asp200= (c.600C>T) is classified Likely benign in SIX5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-10). Very rare (popmax 0.00267%, afr); Associated with branchiootorenal syndrome 2.

What condition is associated with SIX5 p.Asp200= (c.600C>T)?

SIX5 p.Asp200= (c.600C>T) is associated with branchiootorenal syndrome 2 (ClinVar).

How common is SIX5 p.Asp200= (c.600C>T) in the general population?

SIX5 p.Asp200= (c.600C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

SIX5 p.Asp200=

c.600C>T · rs374622328 · VCV1569060

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

branchiootorenal syndrome 2

⚠ 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 3.3	GERP 1, phastCons 1
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,938 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,612,814 alleles · very rare exomes 19/1,460,552 · genomes 5/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,469
European (non-Finnish)	0.00186%	53,619

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.Asp200=
Coding: c.600C>T
MANE Select: NM_175875
dbSNP: rs374622328
Type: single nucleotide variant
Location: chr19:45768245 (GRCh38)

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

Disease context

branchiootorenal syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asp200 (accessed [today's date]).

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