Is AHI1 p.Pro242Ser (c.724C>T) pathogenic?

AHI1 p.Pro242Ser (c.724C>T) is classified Benign/Likely benign in AHI1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0886); Low-frequency (popmax 1.03%, afr); Associated with Joubert syndrome 3.

What condition is associated with AHI1 p.Pro242Ser (c.724C>T)?

AHI1 p.Pro242Ser (c.724C>T) is associated with Joubert syndrome 3, Joubert syndrome (ClinVar).

How common is AHI1 p.Pro242Ser (c.724C>T) in the general population?

AHI1 p.Pro242Ser (c.724C>T) is low-frequency (popmax 1.03%, afr) (gnomAD).

What do computational predictors say about AHI1 p.Pro242Ser (c.724C>T)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

AHI1 p.Pro242Ser

c.724C>T · rs143522987 · VCV260861

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 3

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.31	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 5.2	GERP 0.29, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 202 kb · p 0.67 · regional, not allelic
Overall
CADD	16.34	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 1.03% African / African-American · 730/70,784 alleles

Filtering AF 0.969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.945%

Overall 0.0677% 1,001/1,479,658 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.03%	97
Middle Eastern	0.45%	222
Admixed American	0.134%	749
Remaining individualsnot grpmax-eligible	0.115%	870
European (non-Finnish)	0.0112%	8,952
South Asian	0.00474%	21,091
Finnishnot grpmax-eligible	0.00172%	58,132

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.Pro242Ser
Coding: c.724C>T
MANE Select: NM_001134831
dbSNP: rs143522987
Type: single nucleotide variant
Location: chr6:135465839 (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 242: 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-pro242ser (accessed [today's date]).

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