Is ANXA11 p.Pro30Arg (c.89C>G) pathogenic?

ANXA11 p.Pro30Arg (c.89C>G) is classified Uncertain significance in ANXA11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.2614); Ultra-rare (popmax 0.0274%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANXA11 p.Pro30Arg (c.89C>G)?

ANXA11 p.Pro30Arg (c.89C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ANXA11 p.Pro30Arg (c.89C>G) in the general population?

ANXA11 p.Pro30Arg (c.89C>G) is ultra-rare (popmax 0.0274%, nfe) (gnomAD).

What do computational predictors say about ANXA11 p.Pro30Arg (c.89C>G)?

AlphaMissense predicts likely benign (score 0.2614) — an in-silico prediction, not a clinical call.

ANXA11 p.Pro30Arg

c.89C>G · rs758548370 · VCV2371139

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2614 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2614	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -11.64	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.81, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.87 · regional, not allelic
Overall
CADD	18.95	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 0.0274% European (non-Finnish) · 318/1,160,450 alleles

Filtering AF 0.0249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.023% 361/1,571,844 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0445%	2,249
European (non-Finnish)grpmax	0.0274%	3,649
Finnishnot grpmax-eligible	0.0174%	5,737
African / African-American	0.00684%	14,615

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ANXA11
Protein: p.Pro30Arg
Coding: c.89C>G
MANE Select: NM_145868
dbSNP: rs758548370
Type: single nucleotide variant
Location: chr10:80170882 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.32 · 2 PDB
Residue 30: the 'disordered' region

Full ANXA11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANXA11 p.Ala361Thr Uncertain significance ★★ ⚠ same condition
ANXA11 p.Ala443Asp Uncertain significance ★★ ⚠ same condition
ANXA11 p.Ala58Val Uncertain significance ★★ ⚠ same condition
ANXA11 p.Arg412Gln Uncertain significance ★★ ⚠ same condition
ANXA11 p.Arg461Cys Uncertain significance ★★ ⚠ same condition
ANXA11 p.Arg470Thr Uncertain significance ★★ ⚠ same condition
ANXA11 p.Asp465Gly Uncertain significance ★★ ⚠ same condition
ANXA11 p.Glu397Asp 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/anxa11-p-pro30arg (accessed [today's date]).

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