Is FLG p.Ser1801Pro (c.5401T>C) pathogenic?

FLG p.Ser1801Pro (c.5401T>C) is classified Conflicting classifications of pathogenicity in FLG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-09-01). AlphaMissense: likely benign (0.2919); Ultra-rare (popmax 0.0454%, afr); Associated with Inborn genetic diseases.

What condition is associated with FLG p.Ser1801Pro (c.5401T>C)?

FLG p.Ser1801Pro (c.5401T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Ser1801Pro (c.5401T>C) in the general population?

FLG p.Ser1801Pro (c.5401T>C) is ultra-rare (popmax 0.0454%, afr) (gnomAD).

What do computational predictors say about FLG p.Ser1801Pro (c.5401T>C)?

AlphaMissense predicts likely benign (score 0.2919) — an in-silico prediction, not a clinical call.

FLG p.Ser1801Pro

c.5401T>C · rs373536239 · VCV2359868

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2919 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0454%, afr)

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	0.2919	likely benign
REVEL	0.065	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 -10	GERP -2.6
Regional constraint	o/e 1.77	unconstrained · MANE · 8,404 bp · p 0 · regional, not allelic
Overall
CADD	12.37	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 0.0454% African / African-American · 34/74,882 alleles

Filtering AF 0.0334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0292%

Overall 0.00235% 38/1,613,706 alleles · ultra-rare exomes 16/1,461,814 · genomes 22/151,892 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0454%	2,202
Admixed American	0.00334%	29,984
Remaining individualsnot grpmax-eligible	0.0016%	62,492
European (non-Finnish)	8.47e-05%	1,179,949

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.Ser1801Pro
Coding: c.5401T>C
MANE Select: NM_002016
dbSNP: rs373536239
Type: single nucleotide variant
Location: chr1:152309485 (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-ser1801pro (accessed [today's date]).

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