Is AHI1 p.Arg15Ser (c.43C>A) pathogenic?

AHI1 p.Arg15Ser (c.43C>A) is classified Uncertain significance in AHI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: ambiguous (0.3747); Very rare (popmax 0.00501%, amr); Associated with Inborn genetic diseases.

What condition is associated with AHI1 p.Arg15Ser (c.43C>A)?

AHI1 p.Arg15Ser (c.43C>A) is associated with Inborn genetic diseases (ClinVar).

How common is AHI1 p.Arg15Ser (c.43C>A) in the general population?

AHI1 p.Arg15Ser (c.43C>A) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about AHI1 p.Arg15Ser (c.43C>A)?

AlphaMissense predicts ambiguous (score 0.3747) — an in-silico prediction, not a clinical call.

AHI1 p.Arg15Ser

c.43C>A · VCV4254740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3747	ambiguous
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.92, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 202 kb · p 0.67 · regional, not allelic
Overall
CADD	20.8	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 0.00501% Admixed American · 3/59,878 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000274% 4/1,460,446 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,959
South Asian	0.0011%	90,718

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.Arg15Ser
Coding: c.43C>A
MANE Select: NM_001134831
Type: single nucleotide variant
Location: chr6:135490715 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AHI1 p.Arg15Leu Uncertain significance ★★ ⚠ same residue
AHI1 p.Arg15Cys Uncertain significance ★★ ⚠ same residue
AHI1 p.Arg15His Uncertain significance ★★ ⚠ same residue
AHI1 p.Arg15= Likely benign ★ same residue
AHI1 c.2266+3A>G Uncertain significance ★★ same condition
AHI1 p.Arg1190Gly Uncertain significance ★★ ⚠ same condition
AHI1 p.Arg386Trp Uncertain significance ★★ ⚠ same condition
AHI1 p.Arg565Cys Uncertain significance ★★ ⚠ 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-arg15ser (accessed [today's date]).

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