Is FLG p.Ala1965= (c.5895C>T) pathogenic?

FLG p.Ala1965= (c.5895C>T) is classified Conflicting classifications of pathogenicity in FLG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-07). Ultra-rare (popmax 0.0891%, eas).

How common is FLG p.Ala1965= (c.5895C>T) in the general population?

FLG p.Ala1965= (c.5895C>T) is ultra-rare (popmax 0.0891%, eas) (gnomAD).

FLG p.Ala1965=

c.5895C>T · VCV3765563

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0891%, 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 -5.4	GERP -2.2
Overall
CADD	6.205	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0891% East Asian · 40/44,880 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00923% 149/1,614,140 alleles · ultra-rare exomes 138/1,461,834 · genomes 11/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0891%	1,122
Remaining individualsnot grpmax-eligible	0.0096%	10,417
European (non-Finnish)	0.00822%	12,165
African / African-American	0.00267%	37,522
South Asian	0.0022%	45,536
Admixed American	0.00167%	60,032
Finnishnot grpmax-eligible	0.00156%	64,032

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.Ala1965=
Coding: c.5895C>T
MANE Select: NM_002016
Type: single nucleotide variant
Location: chr1:152308991 (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-ala1965 (accessed [today's date]).

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