Is ANLN p.Ser562= (c.1686G>A) pathogenic?

ANLN p.Ser562= (c.1686G>A) is classified Benign/Likely benign in ANLN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). Low-frequency (popmax 3.62%, afr); Associated with focal segmental glomerulosclerosis 8.

What condition is associated with ANLN p.Ser562= (c.1686G>A)?

ANLN p.Ser562= (c.1686G>A) is associated with focal segmental glomerulosclerosis 8 (ClinVar).

How common is ANLN p.Ser562= (c.1686G>A) in the general population?

ANLN p.Ser562= (c.1686G>A) is low-frequency (popmax 3.62%, afr) (gnomAD).

ANLN p.Ser562=

c.1686G>A · rs34371129 · VCV1170048

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.62%, afr)

Conditions

focal segmental glomerulosclerosis 8

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 -1.3	GERP -3.6
Overall
CADD	12.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.62% African / African-American · 2,719/75,012 alleles

Filtering AF 3.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.46%

Overall 0.194% 3,133/1,614,036 alleles · low-frequency exomes 1,603/1,461,806 · genomes 1,530/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.62%	28
Middle Eastern	0.314%	319
Remaining individualsnot grpmax-eligible	0.246%	406
Admixed American	0.237%	423
South Asian	0.022%	4,554
European (non-Finnish)	0.0067%	14,936

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: ANLN
Protein: p.Ser562=
Coding: c.1686G>A
MANE Select: NM_018685
dbSNP: rs34371129
Type: single nucleotide variant
Location: chr7:36419296 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 60.09 · 3 PDB
Residue 562: the 'interaction with f-actin' region

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

Disease context

focal segmental glomerulosclerosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANLN p.Ser562Leu Uncertain significance ★ ⚠ same residue
ANLN p.Arg431Cys Pathogenic/Likely pathogenic ★★ same condition
ANLN p.Arg376His Uncertain significance ★★ ⚠ same condition
ANLN p.Arg380Cys Uncertain significance ★★ ⚠ same condition
ANLN p.Arg391Cys Uncertain significance ★★ ⚠ same condition
ANLN p.Arg39Gln Uncertain significance ★★ ⚠ same condition
ANLN p.Arg667Cys Uncertain significance ★★ ⚠ same condition
ANLN p.Asn1012Ile Uncertain significance ★★ ⚠ 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/anln-p-ser562 (accessed [today's date]).

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