Is AHI1 p.Arg435= (c.1303C>A) pathogenic?

AHI1 p.Arg435= (c.1303C>A) is classified Likely benign in AHI1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-17). Ultra-rare (popmax 0.0401%, afr); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Arg435= (c.1303C>A)?

AHI1 p.Arg435= (c.1303C>A) is associated with Joubert syndrome, Joubert syndrome 3 (ClinVar).

How common is AHI1 p.Arg435= (c.1303C>A) in the general population?

AHI1 p.Arg435= (c.1303C>A) is ultra-rare (popmax 0.0401%, afr) (gnomAD).

AHI1 p.Arg435=

c.1303C>A · rs121434349 · VCV969396

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, afr)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1
Overall
CADD	15.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% African / African-American · 30/74,796 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.002% 32/1,602,926 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0401%	2,493
Admixed American	0.00169%	59,038
Remaining individualsnot grpmax-eligible	0.00161%	62,028

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: AHI1
Protein: p.Arg435=
Coding: c.1303C>A
MANE Select: NM_001134831
dbSNP: rs121434349
Type: single nucleotide variant
Location: chr6:135455775 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 3

Similar variants

AHI1 p.Arg435Ter Pathogenic ★★ same residue
AHI1 p.Arg435Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
AHI1 p.Arg435Pro Uncertain significance ★ same residue
AHI1 p.Arg435Leu Uncertain significance ★ ⚠ same residue
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

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-arg435 (accessed [today's date]).

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