Is FLG p.Pro1908Ser (c.5722C>T) pathogenic?

FLG p.Pro1908Ser (c.5722C>T) is classified Likely benign in FLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-08). AlphaMissense: likely benign (0.0711); Low-frequency (popmax 1.94%, afr).

How common is FLG p.Pro1908Ser (c.5722C>T) in the general population?

FLG p.Pro1908Ser (c.5722C>T) is low-frequency (popmax 1.94%, afr) (gnomAD).

What do computational predictors say about FLG p.Pro1908Ser (c.5722C>T)?

AlphaMissense predicts likely benign (score 0.0711) — an in-silico prediction, not a clinical call.

FLG p.Pro1908Ser

c.5722C>T · rs141653633 · VCV1206956

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0711 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.94%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

⚠ 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	0.0711	likely benign
REVEL	0.012	strongly 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 -2.4	GERP -2.3
Regional constraint	o/e 1.77	unconstrained · MANE · 8,404 bp · p 0 · regional, not allelic
Overall
CADD	0.009	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 1.94% African / African-American · 1,450/74,744 alleles

Filtering AF 1.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.82%

Overall 0.107% 1,727/1,613,146 alleles · low-frequency exomes 845/1,461,356 · genomes 882/151,790 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.94%	52
Middle Eastern	0.347%	288
Remaining individualsnot grpmax-eligible	0.152%	658
Admixed American	0.14%	714
South Asian	0.0176%	5,690
European (non-Finnish)	0.00509%	19,660
East Asian	0.00223%	44,784

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.Pro1908Ser
Coding: c.5722C>T
MANE Select: NM_002016
dbSNP: rs141653633
Type: single nucleotide variant
Location: chr1:152309164 (GRCh38)

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

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-pro1908ser (accessed [today's date]).

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