Is FASN p.Pro887= (c.2661C>T) pathogenic?

FASN p.Pro887= (c.2661C>T) is classified Likely benign in FASN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-24). Rare (popmax 0.181%, mid); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Pro887= (c.2661C>T)?

FASN p.Pro887= (c.2661C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Pro887= (c.2661C>T) in the general population?

FASN p.Pro887= (c.2661C>T) is rare (popmax 0.181%, mid) (gnomAD).

FASN p.Pro887=

c.2661C>T · rs564814781 · VCV531175

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.181%, mid)

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.3	GERP -2.9
Overall
CADD	0.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.181% Middle Eastern · 11/6,062 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.00926% 149/1,609,464 alleles · rare exomes 130/1,457,118 · genomes 19/152,346 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.181%	551
Admixed American	0.0383%	2,609
Remaining individualsnot grpmax-eligible	0.0128%	7,808
South Asian	0.0121%	8,280
European (non-Finnish)	0.00788%	12,688
African / African-American	0.00266%	37,530
East Asian	0.00223%	44,884

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.Pro887=
Coding: c.2661C>T
MANE Select: NM_004104
dbSNP: rs564814781
Type: single nucleotide variant
Location: chr17:82088240 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 887: the pks/mfas dh domain; the 'n-terminal hotdog fold' 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 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
FASN p.Ala1686Thr 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-pro887 (accessed [today's date]).

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