Is SIX5 p.Ala6Ser (c.16G>T) pathogenic?

SIX5 p.Ala6Ser (c.16G>T) is classified Uncertain significance in SIX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely benign (0.1169); No allele count reported in gnomAD v4.1 (AN 1,531,582).

How common is SIX5 p.Ala6Ser (c.16G>T) in the general population?

SIX5 p.Ala6Ser (c.16G>T) is no allele count reported in gnomAD v4.1 (AN 1,531,582) (gnomAD).

What do computational predictors say about SIX5 p.Ala6Ser (c.16G>T)?

AlphaMissense predicts likely benign (score 0.1169) — an in-silico prediction, not a clinical call.

SIX5 p.Ala6Ser

c.16G>T · rs2513606273 · VCV2534565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1169 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,531,582)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1169	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -7.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 707 bp · p 0.12 · regional, not allelic
Overall
CADD	19.54	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,531,582). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SIX5
Protein: p.Ala6Ser
Coding: c.16G>T
dbSNP: rs2513606273
Type: single nucleotide variant
Location: chr19:45768829 (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-ala6ser (accessed [today's date]).

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