Is FLG p.Ser3922Pro (c.11764T>C) pathogenic?

FLG p.Ser3922Pro (c.11764T>C) is classified Uncertain significance in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely benign (0.1463); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FLG p.Ser3922Pro (c.11764T>C)?

FLG p.Ser3922Pro (c.11764T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Ser3922Pro (c.11764T>C) in the general population?

FLG p.Ser3922Pro (c.11764T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about FLG p.Ser3922Pro (c.11764T>C)?

AlphaMissense predicts likely benign (score 0.1463) — an in-silico prediction, not a clinical call.

FLG p.Ser3922Pro

c.11764T>C · VCV3515701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1463 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1463	likely benign
REVEL	0.089	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 -2	GERP -3.4
Overall
CADD	6.384	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,894 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.Ser3922Pro
Coding: c.11764T>C
Type: single nucleotide variant
Location: chr1:152303122 (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-ser3922pro (accessed [today's date]).

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