Is ACTN4 p.Pro893= (c.2679C>T) pathogenic?

ACTN4 p.Pro893= (c.2679C>T) is classified Benign/Likely benign in ACTN4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-10-17). Rare (popmax 0.591%, eas); Associated with kidney disorder.

What condition is associated with ACTN4 p.Pro893= (c.2679C>T)?

ACTN4 p.Pro893= (c.2679C>T) is associated with kidney disorder, focal segmental glomerulosclerosis 1 (ClinVar).

How common is ACTN4 p.Pro893= (c.2679C>T) in the general population?

ACTN4 p.Pro893= (c.2679C>T) is rare (popmax 0.591%, eas) (gnomAD).

ACTN4 p.Pro893=

c.2679C>T · rs146493523 · VCV585364

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.591%, eas)

Conditions

kidney disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -5.2
Overall
CADD	0.602	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.591% East Asian · 265/44,868 alleles

Filtering AF 0.532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.509%

Overall 0.0232% 374/1,612,754 alleles · rare exomes 317/1,460,568 · genomes 57/152,186 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.591%	169
Middle Eastern	0.099%	1,010
Admixed American	0.0467%	2,143
Remaining individualsnot grpmax-eligible	0.0336%	2,976
South Asian	0.00769%	13,009
European (non-Finnish)	0.00381%	26,222
African / African-American	0.00267%	37,498

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: ACTN4
Protein: p.Pro893=
Coding: c.2679C>T
MANE Select: NM_004924
dbSNP: rs146493523
Type: single nucleotide variant
Location: chr19:38729375 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.66 · 5 PDB
Residue 893: the 'mediates interaction with micall2' region

Full ACTN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 1

Similar variants

ACTN4 p.Pro893Leu Uncertain significance ★ ⚠ same residue
ACTN4 p.Lys255Glu Pathogenic ★★ same condition
ACTN4 c.1443-7C>T Uncertain significance ★★ same condition
ACTN4 c.2190+5G>A Uncertain significance ★★ same condition
ACTN4 c.2190+6C>T Uncertain significance ★★ same condition
ACTN4 p.Ala475Thr Uncertain significance ★★ ⚠ same condition
ACTN4 p.Ala759Thr Uncertain significance ★★ same condition
ACTN4 p.Ala784Val 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/actn4-p-pro893 (accessed [today's date]).

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