Is FA2H p.Pro44fs (c.131del) pathogenic?

FA2H p.Pro44fs (c.131del) is classified Pathogenic in FA2H (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-08). No allele count reported in gnomAD v4.1 (AN 1,515,562); Associated with hereditary spastic paraplegia 35.

What condition is associated with FA2H p.Pro44fs (c.131del)?

FA2H p.Pro44fs (c.131del) is associated with hereditary spastic paraplegia 35 (ClinVar).

How common is FA2H p.Pro44fs (c.131del) in the general population?

FA2H p.Pro44fs (c.131del) is no allele count reported in gnomAD v4.1 (AN 1,515,562) (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.Pro44fs

c.131del · rs2144672539 · VCV1210342

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,515,562)

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 -2.2	GERP -0.82

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,515,562). 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.Pro44fs
Coding: c.131del
MANE Select: NM_024306
dbSNP: rs2144672539
Type: Deletion
Location: chr16:74774625 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.53
Residue 44: 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 p.Pro44Ser Pathogenic/Likely pathogenic ★★ same residue
FA2H c.340_363+8del Pathogenic/Likely pathogenic ★★ same condition
FA2H p.Arg53_Ile58del Pathogenic ★★ same condition
FA2H p.Pro44Gln Pathogenic/Likely pathogenic ★★ same residue
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

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-pro44fs (accessed [today's date]).

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