Is AHI1 p.Arg835= (c.2505G>A) pathogenic?

AHI1 p.Arg835= (c.2505G>A) is classified Benign/Likely benign in AHI1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.01%, mid); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Arg835= (c.2505G>A)?

AHI1 p.Arg835= (c.2505G>A) is associated with Joubert syndrome, Joubert syndrome 3 (ClinVar).

How common is AHI1 p.Arg835= (c.2505G>A) in the general population?

AHI1 p.Arg835= (c.2505G>A) is low-frequency (popmax 1.01%, mid) (gnomAD).

AHI1 p.Arg835=

c.2505G>A · rs41288017 · VCV194870

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.01%, mid)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.171	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.085	GERP 1.5, phastCons 0.53
Overall
CADD	7.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.01% Middle Eastern · 61/6,028 alleles

Filtering AF 0.809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.735%

Overall 0.471% 7,552/1,602,692 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.01%	99
European (non-Finnish)	0.566%	177
Admixed American	0.509%	196
Remaining individualsnot grpmax-eligible	0.406%	246
Ashkenazi Jewishnot grpmax-eligible	0.181%	553
South Asian	0.163%	614
African / African-American	0.112%	890
Finnishnot grpmax-eligible	0.0268%	3,733

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.Arg835=
Coding: c.2505G>A
MANE Select: NM_001134831
dbSNP: rs41288017
Type: single nucleotide variant
Location: chr6:135428747 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.03 · 1 PDB
Residue 835: a UniProt-annotated variant site (in jbts3)

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.Arg835Lys 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
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

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-arg835 (accessed [today's date]).

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