Is FLG p.Asp3497= (c.10491T>C) pathogenic?

FLG p.Asp3497= (c.10491T>C) is classified Benign in FLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). Common (popmax 60%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ichthyosis vulgaris.

What condition is associated with FLG p.Asp3497= (c.10491T>C)?

FLG p.Asp3497= (c.10491T>C) is associated with ichthyosis vulgaris (ClinVar).

FLG p.Asp3497=

Q: How common is FLG p.Asp3497= (c.10491T>C) in the general population?

FLG p.Asp3497= (c.10491T>C) is common (popmax 60%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.10491T>C · rs3126066 · VCV1231010

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 60%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

ichthyosis vulgaris

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 -8.9	GERP -2.9
Overall
CADD	0.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 60% East Asian · 26,670/44,468 alleles

Filtering AF 59.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 59.1%

Overall 20.1% 322,988/1,610,600 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	60%	2
African / African-American	47.4%	2
Admixed American	42.8%	2
South Asian	38.2%	3
Ashkenazi Jewishnot grpmax-eligible	29%	3
Middle Eastern	27.8%	4
Remaining individualsnot grpmax-eligible	24.5%	4
Finnishnot grpmax-eligible	17.1%	6
Amishnot grpmax-eligible	15.6%	6
European (non-Finnish)	13.9%	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: FLG
Protein: p.Asp3497=
Coding: c.10491T>C
MANE Select: NM_002016
dbSNP: rs3126066
Type: single nucleotide variant
Location: chr1:152304395 (GRCh38)

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

Disease context

ichthyosis vulgaris — 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-asp3497 (accessed [today's date]).

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