Is AHI1 p.Pro143Arg (c.428C>G) pathogenic?

AHI1 p.Pro143Arg (c.428C>G) is classified Likely benign in AHI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0888); Rare (popmax 0.178%, eas); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Pro143Arg (c.428C>G)?

AHI1 p.Pro143Arg (c.428C>G) is associated with Joubert syndrome (ClinVar).

How common is AHI1 p.Pro143Arg (c.428C>G) in the general population?

AHI1 p.Pro143Arg (c.428C>G) is rare (popmax 0.178%, eas) (gnomAD).

What do computational predictors say about AHI1 p.Pro143Arg (c.428C>G)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

AHI1 p.Pro143Arg

c.428C>G · rs192524061 · VCV697195

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -4
Regional constraint	o/e 1.01	unconstrained · MANE · 202 kb · p 0.67 · regional, not allelic
Overall
CADD	0.001	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.178% East Asian · 80/44,876 alleles

Filtering AF 0.147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.00527% 85/1,613,768 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.178%	561
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Admixed American	0.00167%	59,978

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.Pro143Arg
Coding: c.428C>G
MANE Select: NM_001134831
dbSNP: rs192524061
Type: single nucleotide variant
Location: chr6:135466135 (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 143: 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AHI1 p.Pro143= Likely benign ★★ same residue
AHI1 p.Pro143Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro143arg (accessed [today's date]).

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