Is FASN p.Phe395= (c.1185C>T) pathogenic?

FASN p.Phe395= (c.1185C>T) is classified Likely benign in FASN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-24). Ultra-rare (popmax 0.0145%, sas); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Phe395= (c.1185C>T)?

FASN p.Phe395= (c.1185C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Phe395= (c.1185C>T) in the general population?

FASN p.Phe395= (c.1185C>T) is ultra-rare (popmax 0.0145%, sas) (gnomAD).

FASN p.Phe395=

c.1185C>T · rs770772130 · VCV1985692

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, sas)

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 Δ0.56 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.6	GERP -3.3
Overall
CADD	1.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0145% South Asian · 13/89,520 alleles

Filtering AF 0.00858% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00672%

Overall 0.00175% 28/1,601,538 alleles · ultra-rare exomes 21/1,449,382 · genomes 7/152,156 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0145%	6,886
African / African-American	0.00803%	12,450
Admixed American	0.00343%	29,129
East Asian	0.00226%	44,236
Finnishnot grpmax-eligible	0.00163%	61,414
European (non-Finnish)	0.000425%	235,038

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.Phe395=
Coding: c.1185C>T
MANE Select: NM_004104
dbSNP: rs770772130
Type: single nucleotide variant
Location: chr17:82091529 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 395: the ketosynthase family 3 (ks3) domain

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-phe395 (accessed [today's date]).

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