Is ANLN p.Phe817Ser (c.2450T>C) pathogenic?

ANLN p.Phe817Ser (c.2450T>C) is classified Uncertain significance in ANLN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely pathogenic (0.8297); Very rare (popmax 0.00221%, sas).

How common is ANLN p.Phe817Ser (c.2450T>C) in the general population?

ANLN p.Phe817Ser (c.2450T>C) is very rare (popmax 0.00221%, sas) (gnomAD).

What do computational predictors say about ANLN p.Phe817Ser (c.2450T>C)?

AlphaMissense predicts likely pathogenic (score 0.8297) — an in-silico prediction, not a clinical call.

ANLN p.Phe817Ser

c.2450T>C · rs1314071720 · VCV1480231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8297 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8297	likely pathogenic
REVEL	0.704	pathogenic-leaning
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.00088 · regional, not allelic
Overall
CADD	26.5	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 0.00221% South Asian · 2/90,694 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,459,850 alleles · very rare

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.Phe817Ser
Coding: c.2450T>C
MANE Select: NM_018685
dbSNP: rs1314071720
Type: single nucleotide variant
Location: chr7:36422783 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 60.09 · 3 PDB
Residue 817: the 'localization to the cleavage furrow' region; an α-helix

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-phe817ser (accessed [today's date]).

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