Is ANLN p.Pro64Arg (c.191C>G) pathogenic?

ANLN p.Pro64Arg (c.191C>G) is classified Uncertain significance in ANLN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-15). AlphaMissense: likely benign (0.2492); Very rare (popmax 0.00671%, nfe); Associated with focal segmental glomerulosclerosis 8.

What condition is associated with ANLN p.Pro64Arg (c.191C>G)?

ANLN p.Pro64Arg (c.191C>G) is associated with focal segmental glomerulosclerosis 8 (ClinVar).

How common is ANLN p.Pro64Arg (c.191C>G) in the general population?

ANLN p.Pro64Arg (c.191C>G) is very rare (popmax 0.00671%, nfe) (gnomAD).

What do computational predictors say about ANLN p.Pro64Arg (c.191C>G)?

AlphaMissense predicts likely benign (score 0.2492) — an in-silico prediction, not a clinical call.

ANLN p.Pro64Arg

c.191C>G · rs200238245 · VCV829977

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2492 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00671%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 8

Computational evidence

Protein change
AlphaMissense	0.2492	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP -1.3, phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.00088 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00671% European (non-Finnish) · 79/1,177,008 alleles

Filtering AF 0.00548% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00507%

Overall 0.00522% 84/1,608,650 alleles · very rare exomes 80/1,456,704 · genomes 4/151,946 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00671%	14,899
Remaining individualsnot grpmax-eligible	0.00321%	31,139
Finnishnot grpmax-eligible	0.00313%	31,958
African / African-American	0.00134%	74,554

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.Pro64Arg
Coding: c.191C>G
MANE Select: NM_018685
dbSNP: rs200238245
Type: single nucleotide variant
Location: chr7:36399097 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 60.09 · 3 PDB
Residue 64: the 'nuclear localization' region; the 'interaction with cd2ap' region; the 'disordered' 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.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
ANLN p.Asp1021Val 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-pro64arg (accessed [today's date]).

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