Is AHI1 p.Ser268= (c.804A>C) pathogenic?

AHI1 p.Ser268= (c.804A>C) is classified Benign/Likely benign in AHI1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.45%, afr); Associated with Joubert syndrome 3.

What condition is associated with AHI1 p.Ser268= (c.804A>C)?

AHI1 p.Ser268= (c.804A>C) is associated with Joubert syndrome 3, Joubert syndrome (ClinVar).

How common is AHI1 p.Ser268= (c.804A>C) in the general population?

AHI1 p.Ser268= (c.804A>C) is low-frequency (popmax 3.45%, afr) (gnomAD).

AHI1 p.Ser268=

c.804A>C · rs35528530 · VCV128328

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.45%, afr)

Conditions

Joubert syndrome 3

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 -0.43	GERP -3.8
Overall
CADD	4.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.45% African / African-American · 2,575/74,602 alleles

Filtering AF 3.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.3%

Overall 0.192% 3,088/1,610,956 alleles · low-frequency exomes 1,591/1,459,572 · genomes 1,497/151,384 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.45%	29
Middle Eastern	0.352%	284
Admixed American	0.317%	315
Remaining individualsnot grpmax-eligible	0.295%	339
South Asian	0.0187%	5,341
European (non-Finnish)	0.00856%	11,678

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.Ser268=
Coding: c.804A>C
MANE Select: NM_001134831
dbSNP: rs35528530
Type: single nucleotide variant
Location: chr6:135463252 (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 268: the 'interaction with hap1' region; the 'disordered' region

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

Also linked: Joubert syndrome

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-ser268 (accessed [today's date]).

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