Is ANLN p.Phe377Ser (c.1130T>C) pathogenic?

ANLN p.Phe377Ser (c.1130T>C) is classified Uncertain significance in ANLN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: likely pathogenic (0.872); Absent from gnomAD v4.1; Associated with focal segmental glomerulosclerosis 8.

What condition is associated with ANLN p.Phe377Ser (c.1130T>C)?

ANLN p.Phe377Ser (c.1130T>C) is associated with focal segmental glomerulosclerosis 8 (ClinVar).

How common is ANLN p.Phe377Ser (c.1130T>C) in the general population?

ANLN p.Phe377Ser (c.1130T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANLN p.Phe377Ser (c.1130T>C)?

AlphaMissense predicts likely pathogenic (score 0.872) — an in-silico prediction, not a clinical call.

ANLN p.Phe377Ser

c.1130T>C · VCV4292296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

focal segmental glomerulosclerosis 8

Computational evidence

Protein change
AlphaMissense	0.872	likely pathogenic · top 10% in ANLN
REVEL	0.33	indeterminate
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.00088 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANLN
Protein: p.Phe377Ser
Coding: c.1130T>C
MANE Select: NM_018685
Type: single nucleotide variant
Location: chr7:36410547 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 60.09 · 3 PDB
Residue 377: 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.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-phe377ser (accessed [today's date]).

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