Is FLG p.Ser287Pro (c.859T>C) pathogenic?

FLG p.Ser287Pro (c.859T>C) is classified Likely benign in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely benign (0.1266); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FLG p.Ser287Pro (c.859T>C)?

FLG p.Ser287Pro (c.859T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Ser287Pro (c.859T>C) in the general population?

FLG p.Ser287Pro (c.859T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about FLG p.Ser287Pro (c.859T>C)?

AlphaMissense predicts likely benign (score 0.1266) — an in-silico prediction, not a clinical call.

FLG p.Ser287Pro

c.859T>C · rs760486851 · VCV3095566

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1266	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4.4	GERP -2.2
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,722 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,884 alleles · very rare

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: FLG
Protein: p.Ser287Pro
Coding: c.859T>C
dbSNP: rs760486851
Type: single nucleotide variant
Location: chr1:152314027 (GRCh38)

Full FLG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/flg-p-ser287pro (accessed [today's date]).

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