Is FLG2 p.Ser617= (c.1851T>C) pathogenic?

FLG2 p.Ser617= (c.1851T>C) is classified Benign in FLG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-04). Common (popmax 72.4%, afr) — too common for a highly-penetrant pathogenic allele.

FLG2 p.Ser617=

Q: How common is FLG2 p.Ser617= (c.1851T>C) in the general population?

FLG2 p.Ser617= (c.1851T>C) is common (popmax 72.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1851T>C · rs6679449 · VCV1182426

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 72.4%, afr) — too common for a highly-penetrant pathogenic allele

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -14	GERP -3.2
Overall
CADD	3.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 72.4% African / African-American · 52,419/72,380 alleles

Filtering AF 71.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 71.7%

Overall 22.7% 360,182/1,588,420 alleles · common exomes 307,272/1,453,166 · genomes 52,910/135,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	72.4%	1
East Asian	46.6%	2
Admixed American	40.2%	2
South Asian	33%	3
Middle Eastern	31.8%	3
Ashkenazi Jewishnot grpmax-eligible	31.2%	3
Amishnot grpmax-eligible	28%	4
Remaining individualsnot grpmax-eligible	26.2%	4
European (non-Finnish)	16.9%	6
Finnishnot grpmax-eligible	15.1%	7

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: FLG2
Protein: p.Ser617=
Coding: c.1851T>C
MANE Select: NM_001014342
dbSNP: rs6679449
Type: single nucleotide variant
Location: chr1:152355935 (GRCh38)

Full FLG2 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/flg2-p-ser617 (accessed [today's date]).

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