Is FLG p.Pro1957= (c.5871T>C) pathogenic?

FLG p.Pro1957= (c.5871T>C) is classified Likely benign in FLG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-16). Rare (popmax 0.165%, amr).

How common is FLG p.Pro1957= (c.5871T>C) in the general population?

FLG p.Pro1957= (c.5871T>C) is rare (popmax 0.165%, amr) (gnomAD).

FLG p.Pro1957=

c.5871T>C · rs550316856 · VCV1298438

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.165%, amr)

⚠ 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 -14	GERP -2.3
Overall
CADD	3.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% Admixed American · 99/60,002 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.0704% 1,136/1,613,396 alleles · rare exomes 986/1,461,214 · genomes 150/152,182 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.165%	606
Ashkenazi Jewishnot grpmax-eligible	0.115%	871
European (non-Finnish)	0.0783%	1,276
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Finnishnot grpmax-eligible	0.0422%	2,371
Middle Eastern	0.0165%	6,062
South Asian	0.011%	9,106
African / African-American	0.004%	25,007
East Asian	0.00223%	44,872

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.Pro1957=
Coding: c.5871T>C
MANE Select: NM_002016
dbSNP: rs550316856
Type: single nucleotide variant
Location: chr1:152309015 (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-pro1957 (accessed [today's date]).

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