Is ANXA11 p.Pro141Arg (c.422C>G) pathogenic?

ANXA11 p.Pro141Arg (c.422C>G) is classified Uncertain significance in ANXA11 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-31). AlphaMissense: likely benign (0.2149); Very rare (popmax 0.000144%).

How common is ANXA11 p.Pro141Arg (c.422C>G) in the general population?

ANXA11 p.Pro141Arg (c.422C>G) is very rare (popmax 0.000144%) (gnomAD).

What do computational predictors say about ANXA11 p.Pro141Arg (c.422C>G)?

AlphaMissense predicts likely benign (score 0.2149) — an in-silico prediction, not a clinical call.

ANXA11 p.Pro141Arg

c.422C>G · rs1210543643 · VCV1977652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2149 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000144%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2149	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -12.01	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 7.2	GERP -0.71, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.87 · regional, not allelic
Overall
CADD	23.2	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 0.000144%

Overall 0.000144% 2/1,385,968 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: ANXA11
Protein: p.Pro141Arg
Coding: c.422C>G
MANE Select: NM_145868
dbSNP: rs1210543643
Type: single nucleotide variant
Location: chr10:80169108 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.32 · 2 PDB
Residue 141: the 'disordered' region

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

Similar variants

ANXA11 p.Asp40Gly Pathogenic ★★ ⚠ same type
ANXA11 p.Asp40Tyr Pathogenic/Likely pathogenic ★★ ⚠ same type
ANXA11 p.Gly38Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
ANXA11 c.171+1G>A Uncertain significance ★★ same type
ANXA11 c.744+2C>T Uncertain significance ★★ same type
ANXA11 c.744+3G>A Uncertain significance ★★ same type
ANXA11 p.Ala361Thr Uncertain significance ★★ ⚠ same type
ANXA11 p.Ala443Asp 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/anxa11-p-pro141arg (accessed [today's date]).

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