Is ANXA11 p.Pro101= (c.303T>C) pathogenic?

ANXA11 p.Pro101= (c.303T>C) is classified Benign in ANXA11 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.71%, nfe).

How common is ANXA11 p.Pro101= (c.303T>C) in the general population?

ANXA11 p.Pro101= (c.303T>C) is low-frequency (popmax 1.71%, nfe) (gnomAD).

ANXA11 p.Pro101=

c.303T>C · rs11542746 · VCV1624066

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.71%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.53, phastCons 1
Overall
CADD	10.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.71% European (non-Finnish) · 20,124/1,177,036 alleles

Filtering AF 1.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.68%

Overall 1.41% 22,727/1,609,518 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.84%	26
European (non-Finnish)grpmax	1.71%	58
Remaining individualsnot grpmax-eligible	1.35%	74
Finnishnot grpmax-eligible	1.15%	87
Ashkenazi Jewishnot grpmax-eligible	0.495%	202
Admixed American	0.493%	203
South Asian	0.384%	261
Middle Eastern	0.341%	294
African / African-American	0.25%	401
East Asian	0.00223%	44,860

Amish 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.Pro101=
Coding: c.303T>C
MANE Select: NM_145868
dbSNP: rs11542746
Type: single nucleotide variant
Location: chr10:80169227 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.32 · 2 PDB
Residue 101: the 'disordered' region

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

Similar variants

ANXA11 p.Pro101Leu Uncertain significance ★ ⚠ same residue
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

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-pro101 (accessed [today's date]).

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