Is GANAB p.Pro443Ser (c.1327C>T) pathogenic?

GANAB p.Pro443Ser (c.1327C>T) is classified Uncertain significance in GANAB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.0888); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GANAB p.Pro443Ser (c.1327C>T)?

GANAB p.Pro443Ser (c.1327C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GANAB p.Pro443Ser (c.1327C>T) in the general population?

GANAB p.Pro443Ser (c.1327C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GANAB p.Pro443Ser (c.1327C>T)?

AlphaMissense predicts likely benign (score 0.0888) — an in-silico prediction, not a clinical call.

GANAB p.Pro443Ser

c.1327C>T · rs1943629764 · VCV2313801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0888 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0888	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 3.3, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 2,437 bp · p 1e-05 · regional, not allelic
Overall
CADD	20.2	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: GANAB
Protein: p.Pro443Ser
Coding: c.1327C>T
MANE Select: NM_198334
dbSNP: rs1943629764
Type: single nucleotide variant
Location: chr11:62630660 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.43 · 2 PDB
Residue 443: a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GANAB c.560+469C>T Uncertain significance ★★ same condition
GANAB p.Arg164Gly Uncertain significance ★★ ⚠ same condition
GANAB p.Arg404Gln Uncertain significance ★★ ⚠ same condition
GANAB p.Arg493Trp Uncertain significance ★★ ⚠ same condition
GANAB p.Arg891Gln Uncertain significance ★★ ⚠ same condition
GANAB p.Asn485Lys Uncertain significance ★★ ⚠ same condition
GANAB p.Cys26Ser Uncertain significance ★★ ⚠ same condition
GANAB p.Gln68His Uncertain significance ★★ ⚠ 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/ganab-p-pro443ser (accessed [today's date]).

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