Is FH p.Phe403fs (c.1209del) pathogenic?

FH p.Phe403fs (c.1209del) is classified Pathogenic/Likely pathogenic in FH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-09-02). No gnomAD frequency available for this variant; Associated with hereditary leiomyomatosis and renal cell cancer.

What condition is associated with FH p.Phe403fs (c.1209del)?

FH p.Phe403fs (c.1209del) is associated with hereditary leiomyomatosis and renal cell cancer, fumaric aciduria, hereditary neoplastic syndrome (ClinVar).

How common is FH p.Phe403fs (c.1209del) in the general population?

FH p.Phe403fs (c.1209del) is no gnomAD frequency available for this variant (gnomAD).

How is Hereditary leiomyomatosis and renal cell cancer inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FH p.Phe403fs

c.1209del · rs1060499644 · VCV393580

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary leiomyomatosis and renal cell cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FH
Protein: p.Phe403fs
Coding: c.1209del
MANE Select: NM_000143
dbSNP: rs1060499644
Type: Deletion
Location: chr1:241502470 (GRCh38)
Gene constraint: LOEUF 0.599 · pLI 0.27 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.92 · 8 PDB

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

Disease context

hereditary leiomyomatosis and renal cell cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fumaric aciduria hereditary neoplastic syndrome

For Hereditary leiomyomatosis and renal cell cancer (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Elderly

Similar variants

FH c.1058_1108+19del Pathogenic ★★ same condition
FH c.1391-2del Pathogenic/Likely pathogenic ★★ same condition
FH c.1392delG Pathogenic ★★ same condition
FH c.267+1_267+10del Pathogenic/Likely pathogenic ★★ same condition
FH c.722_738+3del Pathogenic ★★ same condition
FH c.893_904+7del Pathogenic/Likely pathogenic ★★ same condition
FH c.902_904+4del Likely pathogenic ★★ same condition
FH p.Ala379_Met380insTer 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/fh-p-phe403fs (accessed [today's date]).

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