Is ANXA11 p.Pro75Ser (c.223C>T) pathogenic?

ANXA11 p.Pro75Ser (c.223C>T) is classified Uncertain significance in ANXA11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.1006); Absent from gnomAD v4.1; Associated with amyotrophic lateral sclerosis type 23.

What condition is associated with ANXA11 p.Pro75Ser (c.223C>T)?

ANXA11 p.Pro75Ser (c.223C>T) is associated with amyotrophic lateral sclerosis type 23 (ClinVar).

How common is ANXA11 p.Pro75Ser (c.223C>T) in the general population?

ANXA11 p.Pro75Ser (c.223C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANXA11 p.Pro75Ser (c.223C>T)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

ANXA11 p.Pro75Ser

c.223C>T · VCV4531569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

amyotrophic lateral sclerosis type 23

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -9.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 0.47, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.87 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: ANXA11
Protein: p.Pro75Ser
Coding: c.223C>T
MANE Select: NM_145868
Type: single nucleotide variant
Location: chr10:80169307 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.32 · 2 PDB

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

Disease context

amyotrophic lateral sclerosis type 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANXA11 p.Asp40Gly Pathogenic ★★ ⚠ same condition
ANXA11 p.Asp40Tyr Pathogenic/Likely pathogenic ★★ ⚠ same condition
ANXA11 p.Gly38Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
ANXA11 c.744+2C>T Uncertain significance ★★ same condition
ANXA11 p.Arg302Cys Uncertain significance ★★ ⚠ same condition
ANXA11 p.Arg461His Uncertain significance ★★ ⚠ same condition
ANXA11 p.Arg475Gln Uncertain significance ★★ ⚠ same condition
ANXA11 p.Pro108Ser Benign/Likely benign ★★ ⚠ 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-pro75ser (accessed [today's date]).

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