Is ANXA11 p.Ser95fs (c.282dup) pathogenic?

ANXA11 p.Ser95fs (c.282dup) is classified Uncertain significance in ANXA11 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-20). Ultra-rare (popmax 0.0111%, eas).

How common is ANXA11 p.Ser95fs (c.282dup) in the general population?

ANXA11 p.Ser95fs (c.282dup) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

ANXA11 p.Ser95fs

c.282dup · rs759677084 · VCV1376315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -2.3, phastCons 0.89
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,852 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00267% 43/1,611,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,970
Admixed American	0.00501%	19,974
African / African-American	0.004%	24,986
Remaining individualsnot grpmax-eligible	0.00321%	31,178
European (non-Finnish)	0.00237%	42,125
South Asian	0.0022%	45,499

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.Ser95fs
Coding: c.282dup
MANE Select: NM_145868
dbSNP: rs759677084
Type: Duplication
Location: chr10:80169247 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.32 · 2 PDB
Residue 95: the 'disordered' region

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

Similar variants

ANXA11 p.Gly137fs Uncertain significance ★ same type
ANXA11 p.Lys378fs Uncertain significance ★ same type
ANXA11 c.1181-9dup Likely benign ★ same type
ANXA11 c.745-40dup Benign ★ same type
ANXA11 p.Met1fs Likely benign ★ same type
ANXA11 p.Val158_Pro159insThrTyrProGlyGlnProProVal 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-ser95fs (accessed [today's date]).

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