Is SIX5 p.Asp162= (c.486C>T) pathogenic?

SIX5 p.Asp162= (c.486C>T) is classified Likely benign in SIX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-19). Ultra-rare (popmax 0.0154%, amr).

How common is SIX5 p.Asp162= (c.486C>T) in the general population?

SIX5 p.Asp162= (c.486C>T) is ultra-rare (popmax 0.0154%, amr) (gnomAD).

SIX5 p.Asp162=

c.486C>T · VCV3607290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, amr)

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 1.8	GERP -3.7, phastCons 1
Overall
CADD	10.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% Admixed American · 9/58,256 alleles

Filtering AF 0.00804% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00594%

Overall 0.002% 32/1,596,352 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0154%	6,473
South Asian	0.00669%	14,938
Remaining individualsnot grpmax-eligible	0.00324%	30,887
East Asian	0.00225%	44,384
African / African-American	0.00134%	74,718
European (non-Finnish)	0.00111%	90,315

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.Asp162=
Coding: c.486C>T
Type: single nucleotide variant
Location: chr19:45768359 (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-asp162 (accessed [today's date]).

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