Is AHI1 p.Ser454= (c.1362C>T) pathogenic?

AHI1 p.Ser454= (c.1362C>T) is classified Likely benign in AHI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-22). Very rare (popmax 0.00598%, sas); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Ser454= (c.1362C>T)?

AHI1 p.Ser454= (c.1362C>T) is associated with Joubert syndrome (ClinVar).

How common is AHI1 p.Ser454= (c.1362C>T) in the general population?

AHI1 p.Ser454= (c.1362C>T) is very rare (popmax 0.00598%, sas) (gnomAD).

AHI1 p.Ser454=

c.1362C>T · rs760276355 · VCV699903

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00598%, sas)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP 0.99, phastCons 1
Overall
CADD	12.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00598% South Asian · 5/83,616 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00147%

Overall 0.000644% 10/1,553,586 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00598%	16,723
Ashkenazi Jewishnot grpmax-eligible	0.00348%	28,702
Admixed American	0.00195%	51,388
European (non-Finnish)	0.000261%	382,561

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.Ser454=
Coding: c.1362C>T
MANE Select: NM_001134831
dbSNP: rs760276355
Type: single nucleotide variant
Location: chr6:135453419 (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

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.2623+1G>A Pathogenic ★★ same condition
AHI1 c.2623+1G>T Pathogenic ★★ same condition
AHI1 c.3426+2T>C 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-ser454 (accessed [today's date]).

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