Is AQP11 p.Pro233Ser (c.697C>T) pathogenic?

AQP11 p.Pro233Ser (c.697C>T) is classified Uncertain significance in AQP11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely benign (0.0765); Very rare (popmax 0.000509%, nfe).

How common is AQP11 p.Pro233Ser (c.697C>T) in the general population?

AQP11 p.Pro233Ser (c.697C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about AQP11 p.Pro233Ser (c.697C>T)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

AQP11 p.Pro233Ser

c.697C>T · VCV3935523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.91	GERP -3.2, phastCons 0.001
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.94 · regional, not allelic
Overall
CADD	0.414	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

Grpmax group 0.000509% European (non-Finnish) · 6/1,177,730 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000373% 6/1,608,044 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: AQP11
Protein: p.Pro233Ser
Coding: c.697C>T
MANE Select: NM_173039
Type: single nucleotide variant
Location: chr11:77603633 (GRCh38)
Gene constraint: LOEUF 1.743 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.82 · 1 PDB

Full AQP11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AQP11 p.Pro233Leu Likely benign ★ same residue
AQP11 p.Pro100Leu Uncertain significance ★★ ⚠ same type
AQP11 p.Ala171Thr Uncertain significance ★ ⚠ same type
AQP11 p.Ala180Thr Uncertain significance ★ ⚠ same type
AQP11 p.Arg120Lys Uncertain significance ★ ⚠ same type
AQP11 p.Arg188Gln Uncertain significance ★ ⚠ same type
AQP11 p.Arg41Gly Uncertain significance ★ ⚠ same type
AQP11 p.Arg8Gly 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/aqp11-p-pro233ser (accessed [today's date]).

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