Is FH p.Arg3fs (c.7del) pathogenic?

FH p.Arg3fs (c.7del) is classified Uncertain significance in FH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). Associated with hereditary neoplastic syndrome.

What condition is associated with FH p.Arg3fs (c.7del)?

FH p.Arg3fs (c.7del) is associated with hereditary neoplastic syndrome (ClinVar).

FH p.Arg3fs

c.7del · VCV3515072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

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 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.11	GERP -1, phastCons 0.004

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

Variant & gene context

Gene: FH
Protein: p.Arg3fs
Coding: c.7del
MANE Select: NM_000143
Type: Deletion
Location: chr1:241519716 (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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FH p.Arg3Gln Uncertain significance ★★ ⚠ same residue
FH p.Arg3Pro Uncertain significance ★★ ⚠ same residue
FH p.Arg3Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
FH p.Arg3Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
FH p.Arg3= Likely benign ★ same residue
FH c.1058_1108+19del Pathogenic ★★ same condition
FH c.1392delG Pathogenic ★★ same condition
FH c.267+1_267+10del Pathogenic/Likely 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-arg3fs (accessed [today's date]).

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