Is FA2H p.Phe39fs (c.115_121del) pathogenic?

FA2H p.Phe39fs (c.115121del) is classified Likely pathogenic in FA2H (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-20). No gnomAD frequency available for this variant; Associated with hereditary spastic paraplegia 35.

What condition is associated with FA2H p.Phe39fs (c.115_121del)?

FA2H p.Phe39fs (c.115_121del) is associated with hereditary spastic paraplegia 35 (ClinVar).

How common is FA2H p.Phe39fs (c.115_121del) in the general population?

FA2H p.Phe39fs (c.115_121del) is no gnomAD frequency available for this variant (gnomAD).

How is Autosomal recessive spastic paraplegia type 35 inherited?

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

FA2H p.Phe39fs

c.115_121del · rs2144672568 · VCV1684571

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary spastic paraplegia 35

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 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.1	GERP -0.5, 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: FA2H
Protein: p.Phe39fs
Coding: c.115_121del
MANE Select: NM_024306
dbSNP: rs2144672568
Type: Deletion
Location: chr16:74774635 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.53
Residue 39: the cytochrome b5 heme-binding domain

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

Disease context

hereditary spastic paraplegia 35 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 35 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

FA2H c.340_363+8del Pathogenic/Likely pathogenic ★★ same condition
FA2H p.Arg53_Ile58del Pathogenic ★★ same condition
FA2H p.Pro44fs Pathogenic ★★ same condition
FA2H p.Thr314fs Pathogenic/Likely pathogenic ★★ same condition
FA2H p.Tyr170_Ser171delinsTer Pathogenic ★★ same condition
FA2H p.Val275fs Pathogenic/Likely pathogenic ★★ same condition
FA2H p.Arg32fs Likely pathogenic ★ same condition
FA2H p.Gly194fs 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/fa2h-p-phe39fs (accessed [today's date]).

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