Is FLG p.Ser3935Pro (c.11803T>C) pathogenic?

FLG p.Ser3935Pro (c.11803T>C) is classified Benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-09). AlphaMissense: likely benign (0.1327); Common (popmax 34.5%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about FLG p.Ser3935Pro (c.11803T>C)?

AlphaMissense predicts likely benign (score 0.1327) — an in-silico prediction, not a clinical call.

FLG p.Ser3935Pro

Q: How common is FLG p.Ser3935Pro (c.11803T>C) in the general population?

FLG p.Ser3935Pro (c.11803T>C) is common (popmax 34.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.11803T>C · rs3126065 · VCV1258538

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1327 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 34.5%, afr) — too common for a highly-penetrant pathogenic allele

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	0.1327	likely benign
REVEL	0.126	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 -1.2	GERP -2.5
Regional constraint	o/e 1.38	unconstrained · MANE · 2,903 bp · p 2.8e-40 · regional, not allelic
Overall
CADD	16.01	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 34.5% African / African-American · 25,870/74,944 alleles

Filtering AF 34.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 34%

Overall 1.83% 29,527/1,614,054 alleles · common exomes 14,594/1,461,884 · genomes 14,933/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	34.5%	3
Remaining individualsnot grpmax-eligible	2.19%	46
Admixed American	2.09%	48
Middle Eastern	1.14%	88
Ashkenazi Jewishnot grpmax-eligible	0.159%	630
South Asian	0.0955%	1,047
European (non-Finnish)	0.0702%	1,425
East Asian	0.00223%	44,878
Finnishnot grpmax-eligible	0.00156%	64,034

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.Ser3935Pro
Coding: c.11803T>C
MANE Select: NM_002016
dbSNP: rs3126065
Type: single nucleotide variant
Location: chr1:152303083 (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-ser3935pro (accessed [today's date]).

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