Is FASN p.Pro617= (c.1851G>A) pathogenic?

FASN p.Pro617= (c.1851G>A) is classified Benign in FASN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). Ultra-rare (popmax 0.0174%, mid); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Pro617= (c.1851G>A)?

FASN p.Pro617= (c.1851G>A) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Pro617= (c.1851G>A) in the general population?

FASN p.Pro617= (c.1851G>A) is ultra-rare (popmax 0.0174%, mid) (gnomAD).

FASN p.Pro617=

c.1851G>A · rs766299074 · VCV1601776

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, mid)

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 -20	GERP -3.1
Overall
CADD	0.244	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% Middle Eastern · 1/5,760 alleles

Filtering AF 0.00216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.016% 255/1,592,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.364%	275
Middle Easterngrpmax	0.0174%	5,760
Remaining individualsnot grpmax-eligible	0.013%	7,700
South Asian	0.00567%	17,624
African / African-American	0.00536%	18,666
East Asian	0.00227%	44,072
European (non-Finnish)	0.0012%	83,661

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro617=
Coding: c.1851G>A
MANE Select: NM_004104
dbSNP: rs766299074
Type: single nucleotide variant
Location: chr17:82090394 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 617: an α-helix; the 'acyl and malonyl transferases' 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.Pro617Thr Uncertain significance ★★ ⚠ same residue
FASN p.Pro617Leu Likely benign ★★ same residue
FASN p.Pro617Arg 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

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-pro617 (accessed [today's date]).

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