Is FLG2 p.Asp195= (c.585C>T) pathogenic?

FLG2 p.Asp195= (c.585C>T) is classified Likely benign in FLG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-08). Rare (popmax 0.297%, mid).

How common is FLG2 p.Asp195= (c.585C>T) in the general population?

FLG2 p.Asp195= (c.585C>T) is rare (popmax 0.297%, mid) (gnomAD).

FLG2 p.Asp195=

c.585C>T · rs142857077 · VCV2639337

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.297%, mid)

⚠ 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 -2.6	GERP -3.9
Overall
CADD	2.996	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.297% Middle Eastern · 18/6,062 alleles

Filtering AF 0.192% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.159%

Overall 0.0802% 1,295/1,614,184 alleles · rare exomes 1,187/1,461,890 · genomes 108/152,294 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.297%	337
Ashkenazi Jewishnot grpmax-eligible	0.172%	580
Remaining individualsnot grpmax-eligible	0.125%	801
Admixed American	0.112%	896
European (non-Finnish)	0.089%	1,124
South Asian	0.0264%	3,795
African / African-American	0.00799%	12,509
Finnishnot grpmax-eligible	0.00156%	64,034

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.Asp195=
Coding: c.585C>T
MANE Select: NM_001014342
dbSNP: rs142857077
Type: single nucleotide variant
Location: chr1:152357201 (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-asp195 (accessed [today's date]).

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