Is FA2H p.Thr299fs (c.893dup) pathogenic?

FA2H p.Thr299fs (c.893dup) is classified Pathogenic in FA2H (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-02). Very rare (popmax 6.2e-05%).

How common is FA2H p.Thr299fs (c.893dup) in the general population?

FA2H p.Thr299fs (c.893dup) is very rare (popmax 6.2e-05%) (gnomAD).

FA2H p.Thr299fs

c.893dup · VCV3381147

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP -0.65, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,750 alleles · very rare exomes 1/1,461,752 · genomes 0/151,998 · joint denominator

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: FA2H
Protein: p.Thr299fs
Coding: c.893dup
MANE Select: NM_024306
Type: Duplication
Location: chr16:74716492 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.53
Residue 299: the fatty acid hydroxylase domain

Full FA2H gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FA2H p.Thr299Ala Uncertain significance ★ ⚠ same residue
FA2H p.Thr299Ser Uncertain significance ★ ⚠ same residue
FAAH p.Cys299= Benign ★ same residue
FA2H p.Leu305fs Pathogenic ★★ same type
FA2H p.Ala24fs Likely pathogenic ★ same type
FA2H p.Ile58fs Pathogenic ★ same type
FA2H p.Met220fs Likely pathogenic ★ same type
FA2H p.Phe236fs Likely pathogenic ★ 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/fa2h-p-thr299fs (accessed [today's date]).

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