Is FASN p.Pro2389= (c.7167G>A) pathogenic?

FASN p.Pro2389= (c.7167G>A) is classified Benign in FASN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Rare (popmax 0.245%, afr); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Pro2389= (c.7167G>A)?

FASN p.Pro2389= (c.7167G>A) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Pro2389= (c.7167G>A) in the general population?

FASN p.Pro2389= (c.7167G>A) is rare (popmax 0.245%, afr) (gnomAD).

FASN p.Pro2389=

c.7167G>A · rs143485066 · VCV462106

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.245%, afr)

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.9
Overall
CADD	0.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.245% African / African-American · 184/75,064 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.205%

Overall 0.0159% 254/1,601,382 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.245%	408
Middle Eastern	0.066%	1,515
Remaining individualsnot grpmax-eligible	0.0208%	4,797
Admixed American	0.0167%	6,000
European (non-Finnish)	0.00348%	28,775
East Asian	0.00223%	44,868
South Asian	0.0011%	91,068

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: FASN
Protein: p.Pro2389=
Coding: c.7167G>A
MANE Select: NM_004104
dbSNP: rs143485066
Type: single nucleotide variant
Location: chr17:82079588 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 2389: the 'thioesterase' region

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

Disease context

Epileptic encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FASN p.Pro2389Leu Uncertain significance ★★ ⚠ same residue
FASN c.3733-3C>T Uncertain significance ★★ same condition
FASN c.655+3G>T Uncertain significance ★★ same condition
FASN p.Ala1073Ser Uncertain significance ★★ ⚠ same condition
FASN p.Ala1272Val Uncertain significance ★★ ⚠ same condition
FASN p.Ala1285Val Uncertain significance ★★ ⚠ same condition
FASN p.Ala1569Ser Uncertain significance ★★ ⚠ same condition
FASN p.Ala1684Thr Uncertain significance ★★ 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/fasn-p-pro2389 (accessed [today's date]).

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