Is AHI1 p.Ser437Phe (c.1310C>T) pathogenic?

AHI1 p.Ser437Phe (c.1310C>T) is classified Uncertain significance in AHI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-02). AlphaMissense: likely benign (0.0852); Very rare (popmax 0.00401%, afr); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Ser437Phe (c.1310C>T)?

AHI1 p.Ser437Phe (c.1310C>T) is associated with Joubert syndrome, Joubert syndrome 3 (ClinVar).

How common is AHI1 p.Ser437Phe (c.1310C>T) in the general population?

AHI1 p.Ser437Phe (c.1310C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about AHI1 p.Ser437Phe (c.1310C>T)?

AlphaMissense predicts likely benign (score 0.0852) — an in-silico prediction, not a clinical call.

AHI1 p.Ser437Phe

c.1310C>T · rs372919026 · VCV1347277

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0852 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.0852	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -9.12	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 2.6	GERP -2.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 202 kb · p 0.67 · regional, not allelic
Overall
CADD	12.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,878 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000249% 4/1,603,878 alleles · very rare exomes 4/1,451,620 · genomes 0/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,959
Remaining individualsnot grpmax-eligible	0.00161%	62,108

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.Ser437Phe
Coding: c.1310C>T
MANE Select: NM_001134831
dbSNP: rs372919026
Type: single nucleotide variant
Location: chr6:135455768 (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

Also linked: Joubert syndrome 3

Similar variants

AHI1 p.Ser437= 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.2493-2A>G 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-ser437phe (accessed [today's date]).

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