Is AHI1 p.Ser24= (c.72T>C) pathogenic?

AHI1 p.Ser24= (c.72T>C) is classified Benign/Likely benign in AHI1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-03-01). Rare (popmax 0.474%, afr); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Ser24= (c.72T>C)?

AHI1 p.Ser24= (c.72T>C) is associated with Joubert syndrome (ClinVar).

How common is AHI1 p.Ser24= (c.72T>C) in the general population?

AHI1 p.Ser24= (c.72T>C) is rare (popmax 0.474%, afr) (gnomAD).

AHI1 p.Ser24=

c.72T>C · rs73777558 · VCV128321

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.474%, 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 4.9	GERP -0.79, phastCons 1
Overall
CADD	7.727	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.474% African / African-American · 356/75,030 alleles

Filtering AF 0.434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.418%

Overall 0.0251% 405/1,613,382 alleles · rare exomes 199/1,461,076 · genomes 206/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.474%	211
Admixed American	0.0383%	2,608
Remaining individualsnot grpmax-eligible	0.0272%	3,674
Middle Eastern	0.0165%	6,058
South Asian	0.0011%	91,058
European (non-Finnish)	0.000593%	168,495

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.Ser24=
Coding: c.72T>C
MANE Select: NM_001134831
dbSNP: rs73777558
Type: single nucleotide variant
Location: chr6:135490686 (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 p.Ser24Gly Uncertain significance ★ ⚠ same residue
AHI1 p.Ser24fs Pathogenic/Likely pathogenic ★★ 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.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-ser24 (accessed [today's date]).

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