Is FASN p.Pro1985Ser (c.5953C>T) pathogenic?

FASN p.Pro1985Ser (c.5953C>T) is classified Uncertain significance in FASN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-03). AlphaMissense: likely benign (0.1517); Very rare (popmax 0.00223%, eas); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Pro1985Ser (c.5953C>T)?

FASN p.Pro1985Ser (c.5953C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Pro1985Ser (c.5953C>T) in the general population?

FASN p.Pro1985Ser (c.5953C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about FASN p.Pro1985Ser (c.5953C>T)?

AlphaMissense predicts likely benign (score 0.1517) — an in-silico prediction, not a clinical call.

FASN p.Pro1985Ser

c.5953C>T · rs1206085529 · VCV647289

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1517 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.1517	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 5,668 bp · p 2e-08 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Overall 6.2e-05% 1/1,612,888 alleles · very rare exomes 1/1,460,564 · genomes 0/152,324 · joint denominator

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.Pro1985Ser
Coding: c.5953C>T
MANE Select: NM_004104
dbSNP: rs1206085529
Type: single nucleotide variant
Location: chr17:82082381 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 1985: an α-helix; the 'beta-ketoacyl reductase' 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-pro1985ser (accessed [today's date]).

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