Is ANLN p.Ser800Phe (c.2399C>T) pathogenic?

ANLN p.Ser800Phe (c.2399C>T) is classified Uncertain significance in ANLN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-18). AlphaMissense: likely pathogenic (0.6491); Very rare (popmax 0.00017%, nfe).

How common is ANLN p.Ser800Phe (c.2399C>T) in the general population?

ANLN p.Ser800Phe (c.2399C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ANLN p.Ser800Phe (c.2399C>T)?

AlphaMissense predicts likely pathogenic (score 0.6491) — an in-silico prediction, not a clinical call.

ANLN p.Ser800Phe

c.2399C>T · rs2534630101 · VCV2113853

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6491 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6491	likely pathogenic
REVEL	0.279	benign-leaning
SaProt	LLR -9.43	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.00088 · regional, not allelic
Overall
CADD	26.2	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,800 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,596 alleles · very rare exomes 2/1,461,334 · genomes 0/152,262 · joint denominator

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.Ser800Phe
Coding: c.2399C>T
MANE Select: NM_018685
dbSNP: rs2534630101
Type: single nucleotide variant
Location: chr7:36422732 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 60.09 · 3 PDB
Residue 800: the 'localization to the cleavage furrow' region

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

Similar variants

ANLN p.Arg431Cys Pathogenic/Likely pathogenic ★★ same type
ANLN c.2653-13G>A Uncertain significance ★★ same type
ANLN p.Ala47Gly Uncertain significance ★★ ⚠ same type
ANLN p.Ala828Thr Uncertain significance ★★ ⚠ same type
ANLN p.Ala940Thr Uncertain significance ★★ ⚠ same type
ANLN p.Arg1040His Uncertain significance ★★ ⚠ same type
ANLN p.Arg154Cys Uncertain significance ★★ ⚠ same type
ANLN p.Arg376Cys Uncertain significance ★★ ⚠ same type

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-ser800phe (accessed [today's date]).

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