Is AHI1 p.Ser331= (c.993C>T) pathogenic?

AHI1 p.Ser331= (c.993C>T) is classified Likely benign in AHI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). Very rare (popmax 0.005%, amr); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Ser331= (c.993C>T)?

AHI1 p.Ser331= (c.993C>T) is associated with Joubert syndrome (ClinVar).

How common is AHI1 p.Ser331= (c.993C>T) in the general population?

AHI1 p.Ser331= (c.993C>T) is very rare (popmax 0.005%, amr) (gnomAD).

AHI1 p.Ser331=

c.993C>T · rs992225953 · VCV2976233

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 1.9	GERP -2, phastCons 1
Overall
CADD	5.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,022 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000342% 5/1,461,646 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,007
European (non-Finnish)	0.00017%	589,918

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.Ser331=
Coding: c.993C>T
MANE Select: NM_001134831
dbSNP: rs992225953
Type: single nucleotide variant
Location: chr6:135457652 (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 331: the 'interaction with hap1' region

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.Ser331Asn Likely benign ★★ 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
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-ser331 (accessed [today's date]).

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