Is FLG p.Ala668= (c.2004T>C) pathogenic?

FLG p.Ala668= (c.2004T>C) is classified Likely benign in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-14). Rare (popmax 0.169%, eas).

How common is FLG p.Ala668= (c.2004T>C) in the general population?

FLG p.Ala668= (c.2004T>C) is rare (popmax 0.169%, eas) (gnomAD).

FLG p.Ala668=

c.2004T>C · VCV4912284

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.169%, 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 -0.01	GERP -2.3
Overall
CADD	1.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.169% East Asian · 76/44,840 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.00732% 118/1,612,336 alleles · rare exomes 104/1,460,440 · genomes 14/151,896 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.169%	590
Admixed American	0.005%	20,002
African / African-American	0.00401%	24,962
Finnishnot grpmax-eligible	0.00312%	32,006
European (non-Finnish)	0.0028%	35,712
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Ala668=
Coding: c.2004T>C
MANE Select: NM_002016
Type: single nucleotide variant
Location: chr1:152312882 (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-ala668 (accessed [today's date]).

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