Is FA2H p.Ile233Phe (c.697A>T) pathogenic?

FA2H p.Ile233Phe (c.697A>T) is classified Uncertain significance in FA2H (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.2059); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FA2H p.Ile233Phe (c.697A>T)?

FA2H p.Ile233Phe (c.697A>T) is associated with Inborn genetic diseases (ClinVar).

How common is FA2H p.Ile233Phe (c.697A>T) in the general population?

FA2H p.Ile233Phe (c.697A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FA2H p.Ile233Phe (c.697A>T)?

AlphaMissense predicts likely benign (score 0.2059) — an in-silico prediction, not a clinical call.

FA2H p.Ile233Phe

c.697A>T · VCV4252416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2059 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2059	likely benign
REVEL	0.592	indeterminate
SaProt	LLR -10.75	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.86 · regional, not allelic
Overall
CADD	22.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FA2H
Protein: p.Ile233Phe
Coding: c.697A>T
MANE Select: NM_024306
Type: single nucleotide variant
Location: chr16:74719077 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.53
Residue 233: the fatty acid hydroxylase domain

Full FA2H 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

FA2H p.Ile233= Uncertain significance ★ same residue
FA2H p.Arg189Ter Pathogenic ★★ same condition
FA2H c.363+5C>A Uncertain significance ★★ same condition
FA2H p.Arg151Gly Uncertain significance ★★ ⚠ same condition
FA2H p.Arg28Cys Uncertain significance ★★ ⚠ same condition
FA2H p.Gln289His Uncertain significance ★★ ⚠ same condition
FA2H p.Gln344Glu Uncertain significance ★★ ⚠ same condition
FA2H p.Gln344His 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/fa2h-p-ile233phe (accessed [today's date]).

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