Is FASN p.Arg477= (c.1431C>T) pathogenic?

FASN p.Arg477= (c.1431C>T) is classified Benign/Likely benign in FASN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-30). Rare (popmax 0.223%, sas); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Arg477= (c.1431C>T)?

FASN p.Arg477= (c.1431C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Arg477= (c.1431C>T) in the general population?

FASN p.Arg477= (c.1431C>T) is rare (popmax 0.223%, sas) (gnomAD).

FASN p.Arg477=

c.1431C>T · rs567264906 · VCV1601780

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.223%, sas)

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 -3.2	GERP -3.2
Overall
CADD	3.662	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.223% South Asian · 202/90,670 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.0143% 230/1,608,096 alleles · rare exomes 211/1,455,744 · genomes 19/152,352 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.223%	449
Remaining individualsnot grpmax-eligible	0.0177%	5,657
African / African-American	0.0133%	7,500
Admixed American	0.00167%	59,730
European (non-Finnish)	0.000509%	196,342

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.Arg477=
Coding: c.1431C>T
MANE Select: NM_004104
dbSNP: rs567264906
Type: single nucleotide variant
Location: chr17:82091283 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 477: a β-strand; the 'acyl and malonyl transferases' region; a UniProt-annotated variant site (in)

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.Arg477His Uncertain significance ★ ⚠ same residue
FASN p.Arg477Ser 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

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-arg477 (accessed [today's date]).

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