Is FA2H p.Pro293= (c.879C>T) pathogenic?

FA2H p.Pro293= (c.879C>T) is classified Benign/Likely benign in FA2H (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 83.3%, mid) — too common for a highly-penetrant pathogenic allele; Associated with hereditary spastic paraplegia 35.

What condition is associated with FA2H p.Pro293= (c.879C>T)?

FA2H p.Pro293= (c.879C>T) is associated with hereditary spastic paraplegia 35, hereditary spastic paraplegia (ClinVar).

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.Pro293=

Q: How common is FA2H p.Pro293= (c.879C>T) in the general population?

FA2H p.Pro293= (c.879C>T) is common (popmax 83.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.879C>T · rs2301865 · VCV129031

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 83.3%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary spastic paraplegia 35

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -2.9
Overall
CADD	0.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 83.3% Middle Eastern · 5,051/6,060 alleles

Filtering AF 81.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 81.3%

Overall 79.7% 1,285,307/1,612,910 alleles · common exomes 1,167,962/1,461,230 · genomes 117,345/151,680 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	83.3%	1
Finnishnot grpmax-eligible	83%	1
European (non-Finnish)	81.5%	1
Remaining individualsnot grpmax-eligible	79.2%	1
Ashkenazi Jewishnot grpmax-eligible	79.1%	1
Admixed American	76%	1
Amishnot grpmax-eligible	75.7%	1
African / African-American	71.1%	1
South Asian	70.2%	1
East Asian	65.3%	2

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.Pro293=
Coding: c.879C>T
MANE Select: NM_024306
dbSNP: rs2301865
Type: single nucleotide variant
Location: chr16:74716507 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.53
Residue 293: the fatty acid hydroxylase 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

Also linked: hereditary spastic paraplegia

For Autosomal recessive spastic paraplegia type 35 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

FA2H c.363+2T>C Pathogenic/Likely pathogenic ★★ same condition
FA2H c.506+1G>C Pathogenic/Likely pathogenic ★★ same condition
FA2H c.786+1G>A Pathogenic/Likely pathogenic ★★ same condition
FA2H p.Arg127Ter Pathogenic/Likely pathogenic ★★ same condition
FA2H p.Arg189Ter Pathogenic ★★ same condition
FA2H p.Arg197Ter Pathogenic/Likely pathogenic ★★ same condition
FA2H p.Arg235His Pathogenic/Likely pathogenic ★★ same condition
FA2H p.Arg269His 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/fa2h-p-pro293 (accessed [today's date]).

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