Is FLG p.Ser3039Pro (c.9115T>C) pathogenic?

FLG p.Ser3039Pro (c.9115T>C) is classified Benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-10-05). AlphaMissense: likely benign (0.0593); Common (popmax 12%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about FLG p.Ser3039Pro (c.9115T>C)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

FLG p.Ser3039Pro

Q: How common is FLG p.Ser3039Pro (c.9115T>C) in the general population?

FLG p.Ser3039Pro (c.9115T>C) is common (popmax 12%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9115T>C · rs544832484 · VCV1242771

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 12%, 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	0.0593	likely benign
REVEL	0.02	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 -5	GERP -3
Regional constraint	o/e 0.36	constrained · MANE · 591 bp · p 4.1e-23 · regional, not allelic
Overall
CADD	2.34	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 12% African / African-American · 3,073/25,594 alleles

Filtering AF 11.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.5%

Overall 0.434% 4,722/1,088,672 alleles · common exomes 4,334/1,020,314 · genomes 388/68,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12%	8
Remaining individualsnot grpmax-eligible	0.955%	105
East Asian	0.901%	111
Admixed American	0.628%	159
South Asian	0.609%	164
Middle Eastern	0.404%	247
Ashkenazi Jewishnot grpmax-eligible	0.0575%	1,739
European (non-Finnish)	0.0259%	3,864

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.Ser3039Pro
Coding: c.9115T>C
MANE Select: NM_002016
dbSNP: rs544832484
Type: single nucleotide variant
Location: chr1:152305771 (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-ser3039pro (accessed [today's date]).

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