Is FCSK p.Pro572= (c.1716G>A) pathogenic?

FCSK p.Pro572= (c.1716G>A) is classified Likely benign in FCSK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-13). Ultra-rare (popmax 0.0193%, nfe); Associated with FCSK-related disorder.

What condition is associated with FCSK p.Pro572= (c.1716G>A)?

FCSK p.Pro572= (c.1716G>A) is associated with FCSK-related disorder (ClinVar).

How common is FCSK p.Pro572= (c.1716G>A) in the general population?

FCSK p.Pro572= (c.1716G>A) is ultra-rare (popmax 0.0193%, nfe) (gnomAD).

FCSK p.Pro572=

c.1716G>A · rs763450125 · VCV3054216

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, nfe)

Conditions

FCSK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -13	GERP -3.1
Overall
CADD	0.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% European (non-Finnish) · 220/1,137,734 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0164%

Overall 0.0155% 237/1,526,730 alleles · ultra-rare exomes 228/1,374,546 · genomes 9/152,184 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0193%	5,172
Remaining individualsnot grpmax-eligible	0.0186%	5,375
African / African-American	0.00413%	24,213
Finnishnot grpmax-eligible	0.00402%	24,897
Ashkenazi Jewishnot grpmax-eligible	0.00354%	28,228

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: FCSK
Protein: p.Pro572=
Coding: c.1716G>A
MANE Select: NM_145059
dbSNP: rs763450125
Type: single nucleotide variant
Location: chr16:70473292 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.20

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

Disease context

FCSK-related disorder

Similar variants

FCSK p.Pro572Leu Uncertain significance ★ ⚠ same residue
FCSK p.Arg784Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
FCSK p.Pro375Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
FCSK p.Gln992Ter Uncertain significance same condition
FCSK c.-8T>G Benign same condition
FCSK p.Arg137= Likely benign same condition
FCSK p.Leu154= Likely benign same condition
FCSK p.Leu500= Likely benign same condition

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/fcsk-p-pro572 (accessed [today's date]).

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