Is FARSA p.Pro449= (c.1347C>T) pathogenic?

FARSA p.Pro449= (c.1347C>T) is classified Benign in FARSA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-19). Common (popmax 13.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with FARSA-related disorder.

What condition is associated with FARSA p.Pro449= (c.1347C>T)?

FARSA p.Pro449= (c.1347C>T) is associated with FARSA-related disorder (ClinVar).

FARSA p.Pro449=

Q: How common is FARSA p.Pro449= (c.1347C>T) in the general population?

FARSA p.Pro449= (c.1347C>T) is common (popmax 13.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1347C>T · rs1045913 · VCV3055967

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 13.4%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

FARSA-related disorder

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 -8.7	GERP -2.8
Overall
CADD	0.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.4% Admixed American · 8,016/60,010 alleles

Filtering AF 13.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 13%

Overall 11% 178,196/1,613,960 alleles · common exomes 164,816/1,461,742 · genomes 13,380/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	13.4%	7
European (non-Finnish)	12%	8
Finnishnot grpmax-eligible	11.1%	9
Remaining individualsnot grpmax-eligible	9.99%	10
East Asian	9.05%	11
Ashkenazi Jewishnot grpmax-eligible	8.43%	12
South Asian	7.86%	13
Amishnot grpmax-eligible	5.48%	18
Middle Eastern	5.13%	19
African / African-American	2.1%	48

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: FARSA
Protein: p.Pro449=
Coding: c.1347C>T
MANE Select: NM_004461
dbSNP: rs1045913
Type: single nucleotide variant
Location: chr19:12924192 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.43 · 3 PDB

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

Disease context

FARSA-related disorder

Similar variants

FARSA p.Pro347Leu Likely pathogenic ★★ same condition
FARSA p.Ala283= Benign same condition
FARSA p.Arg271= Likely benign same condition
FARSA p.Gln341Arg Benign same condition
FARSA p.Gly375= Likely benign same condition
FARSA p.Ile471Thr Benign same condition
FARSA p.Val376Leu Benign same condition
FARSA p.Arg338Cys Uncertain significance ★★ ⚠ same type

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/farsa-p-pro449 (accessed [today's date]).

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