Is AOAH p.Leu415Phe (c.1245G>T) pathogenic?

AOAH p.Leu415Phe (c.1245G>T) is classified Likely benign in AOAH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0697); Rare (popmax 0.113%, afr).

How common is AOAH p.Leu415Phe (c.1245G>T) in the general population?

AOAH p.Leu415Phe (c.1245G>T) is rare (popmax 0.113%, afr) (gnomAD).

What do computational predictors say about AOAH p.Leu415Phe (c.1245G>T)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

AOAH p.Leu415Phe

c.1245G>T · VCV4641339

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.113%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -9.04	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 -3.3	GERP -8.6
Regional constraint	o/e 0.94	unconstrained · MANE · 211 kb · p 0.14 · regional, not allelic
Overall
CADD	0.08	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 0.113% African / African-American · 85/75,008 alleles

Filtering AF 0.0938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0867%

Overall 0.00545% 88/1,613,962 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.113%	882
Remaining individualsnot grpmax-eligible	0.0032%	31,251
Admixed American	0.00167%	60,006

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: AOAH
Protein: p.Leu415Phe
Coding: c.1245G>T
MANE Select: NM_001637
Type: single nucleotide variant
Location: chr7:36540380 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.68 · 2 PDB
Residue 415: a disulfide bond; a β-strand

Full AOAH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AOAH p.Ala364Val Uncertain significance ★ ⚠ same type
AOAH p.Ala445Val Uncertain significance ★ ⚠ same type
AOAH p.Ala504Val Uncertain significance ★ ⚠ same type
AOAH p.Ala540Val Uncertain significance ★ ⚠ same type
AOAH p.Arg197Gln Uncertain significance ★ ⚠ same type
AOAH p.Arg202Trp Uncertain significance ★ ⚠ same type
AOAH p.Arg322Cys Uncertain significance ★ ⚠ same type
AOAH p.Arg322Ser Uncertain significance ★ ⚠ same type

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/aoah-p-leu415phe (accessed [today's date]).

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