Is FLG p.Asp52Val (c.155A>T) pathogenic?

FLG p.Asp52Val (c.155A>T) is classified Uncertain significance in FLG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely pathogenic (0.7595); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with FLG p.Asp52Val (c.155A>T)?

FLG p.Asp52Val (c.155A>T) is associated with Inborn genetic diseases (ClinVar).

How common is FLG p.Asp52Val (c.155A>T) in the general population?

FLG p.Asp52Val (c.155A>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about FLG p.Asp52Val (c.155A>T)?

AlphaMissense predicts likely pathogenic (score 0.7595) — an in-silico prediction, not a clinical call.

FLG p.Asp52Val

c.155A>T · rs753416194 · VCV2393468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7595 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

⚠ 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
AlphaMissense	0.7595	likely pathogenic
REVEL	0.204	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 0.99
Regional constraint	o/e 1.77	unconstrained · MANE · 8,404 bp · p 0 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00167% 27/1,613,786 alleles · very rare exomes 25/1,461,580 · genomes 2/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
European (non-Finnish)	0.00203%	49,158
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Asp52Val
Coding: c.155A>T
MANE Select: NM_002016
dbSNP: rs753416194
Type: single nucleotide variant
Location: chr1:152314731 (GRCh38)

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

Disease context

Inborn genetic diseases — 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-asp52val (accessed [today's date]).

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