Is FLG p.Ser3145Pro (c.9433T>C) pathogenic?

FLG p.Ser3145Pro (c.9433T>C) is classified Conflicting classifications of pathogenicity in FLG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-10-17). AlphaMissense: likely benign (0.1718); Ultra-rare (popmax 0.0949%, eas); Associated with Inborn genetic diseases.

What condition is associated with FLG p.Ser3145Pro (c.9433T>C)?

FLG p.Ser3145Pro (c.9433T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Ser3145Pro (c.9433T>C) in the general population?

FLG p.Ser3145Pro (c.9433T>C) is ultra-rare (popmax 0.0949%, eas) (gnomAD).

What do computational predictors say about FLG p.Ser3145Pro (c.9433T>C)?

AlphaMissense predicts likely benign (score 0.1718) — an in-silico prediction, not a clinical call.

FLG p.Ser3145Pro

c.9433T>C · rs551170840 · VCV3095581

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1718 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0949%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1718	likely benign
REVEL	0.023	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
Regional constraint	o/e 1.38	unconstrained · MANE · 2,903 bp · p 2.8e-40 · regional, not allelic
Overall
CADD	1.485	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 0.0949% East Asian · 41/43,226 alleles

Filtering AF 0.0718% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0638%

Overall 0.00277% 44/1,591,026 alleles · ultra-rare exomes 34/1,457,288 · genomes 10/133,738 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0949%	1,054
Admixed American	0.00176%	56,840
Remaining individualsnot grpmax-eligible	0.00161%	61,934
South Asian	0.00112%	89,028

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.Ser3145Pro
Coding: c.9433T>C
MANE Select: NM_002016
dbSNP: rs551170840
Type: single nucleotide variant
Location: chr1:152305453 (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-ser3145pro (accessed [today's date]).

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