Is FLG p.Asp2136= (c.6408C>T) pathogenic?

FLG p.Asp2136= (c.6408C>T) is classified Likely benign in FLG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-05). Low-frequency (popmax 1.03%, eas).

How common is FLG p.Asp2136= (c.6408C>T) in the general population?

FLG p.Asp2136= (c.6408C>T) is low-frequency (popmax 1.03%, eas) (gnomAD).

FLG p.Asp2136=

c.6408C>T · rs779803257 · VCV2639277

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, eas)

⚠ 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 -2.2	GERP -2.5
Overall
CADD	0.904	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.03% East Asian · 462/44,778 alleles

Filtering AF 0.954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.923%

Overall 0.0307% 495/1,613,650 alleles · low-frequency exomes 459/1,461,784 · genomes 36/151,866 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.03%	97
South Asian	0.0165%	6,070
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.00333%	29,993
European (non-Finnish)	0.000509%	196,643

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.Asp2136=
Coding: c.6408C>T
MANE Select: NM_002016
dbSNP: rs779803257
Type: single nucleotide variant
Location: chr1:152308478 (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-asp2136 (accessed [today's date]).

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