Is SIX1 p.Asp179fs (c.531_532del) pathogenic?

SIX1 p.Asp179fs (c.531532del) is classified Uncertain significance in SIX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-12). Very rare (popmax 0.0011%, sas).

How common is SIX1 p.Asp179fs (c.531_532del) in the general population?

SIX1 p.Asp179fs (c.531_532del) is very rare (popmax 0.0011%, sas) (gnomAD).

SIX1 p.Asp179fs

c.531_532del · rs2140240978 · VCV1306414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, 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.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,070 alleles

Overall 6.2e-05% 1/1,614,050 alleles · very rare exomes 1/1,461,702 · genomes 0/152,348 · joint denominator

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: SIX1
Protein: p.Asp179fs
Coding: c.531_532del
MANE Select: NM_005982
dbSNP: rs2140240978
Type: Deletion
Location: chr14:60648658 (GRCh38)

Full SIX1 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/six1-p-asp179fs (accessed [today's date]).

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