Is AHI1 p.Ser6Arg (c.18T>A) pathogenic?

AHI1 p.Ser6Arg (c.18T>A) is classified Uncertain significance in AHI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-18). AlphaMissense: likely pathogenic (0.6025); Absent from gnomAD v4.1; Associated with Joubert syndrome 3.

What condition is associated with AHI1 p.Ser6Arg (c.18T>A)?

AHI1 p.Ser6Arg (c.18T>A) is associated with Joubert syndrome 3 (ClinVar).

How common is AHI1 p.Ser6Arg (c.18T>A) in the general population?

AHI1 p.Ser6Arg (c.18T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AHI1 p.Ser6Arg (c.18T>A)?

AlphaMissense predicts likely pathogenic (score 0.6025) — an in-silico prediction, not a clinical call.

AHI1 p.Ser6Arg

c.18T>A · VCV3593199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6025 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 3

Computational evidence

Protein change
AlphaMissense	0.6025	likely pathogenic
REVEL	0.149	moderately benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 202 kb · p 0.67 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AHI1
Protein: p.Ser6Arg
Coding: c.18T>A
MANE Select: NM_001134831
Type: single nucleotide variant
Location: chr6:135490740 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.03 · 1 PDB

Full AHI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AHI1 c.1152-1G>A Pathogenic/Likely pathogenic ★★ same condition
AHI1 c.1152-2A>G Pathogenic ★★ same condition
AHI1 c.1626+1G>A Pathogenic/Likely pathogenic ★★ same condition
AHI1 c.1779+1G>T Pathogenic/Likely pathogenic ★★ same condition
AHI1 c.2492+1G>A Pathogenic/Likely pathogenic ★★ same condition
AHI1 c.2493-2A>G Pathogenic/Likely pathogenic ★★ same condition
AHI1 c.2623+1G>A Pathogenic ★★ same condition
AHI1 c.2623+1G>T Pathogenic ★★ same condition

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/ahi1-p-ser6arg (accessed [today's date]).

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