Is FLG p.Pro144Ser (c.430C>T) pathogenic?

FLG p.Pro144Ser (c.430C>T) is classified Uncertain significance in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.2513); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FLG p.Pro144Ser (c.430C>T)?

FLG p.Pro144Ser (c.430C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Pro144Ser (c.430C>T) in the general population?

FLG p.Pro144Ser (c.430C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLG p.Pro144Ser (c.430C>T)?

AlphaMissense predicts likely benign (score 0.2513) — an in-silico prediction, not a clinical call.

FLG p.Pro144Ser

c.430C>T · rs2525221347 · VCV2250801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2513 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2513	likely benign
REVEL	0.048	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 -0.8	GERP -4
Overall
CADD	4.356	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLG
Protein: p.Pro144Ser
Coding: c.430C>T
dbSNP: rs2525221347
Type: single nucleotide variant
Location: chr1:152314456 (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-pro144ser (accessed [today's date]).

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