Is APBB1IP p.Ser438Pro (c.1312T>C) pathogenic?

APBB1IP p.Ser438Pro (c.1312T>C) is classified Uncertain significance in APBB1IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.204); Very rare (popmax 0.00268%, afr).

How common is APBB1IP p.Ser438Pro (c.1312T>C) in the general population?

APBB1IP p.Ser438Pro (c.1312T>C) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about APBB1IP p.Ser438Pro (c.1312T>C)?

AlphaMissense predicts likely benign (score 0.204) — an in-silico prediction, not a clinical call.

APBB1IP p.Ser438Pro

c.1312T>C · VCV4641587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.204 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.204	likely benign
REVEL	0.287	benign-leaning
SaProt	LLR -12.66	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 6,746 bp · p 0.12 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,592 alleles

Filtering AF 0.000445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000124% 2/1,609,966 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: APBB1IP
Protein: p.Ser438Pro
Coding: c.1312T>C
MANE Select: NM_019043
Type: single nucleotide variant
Location: chr10:26560787 (GRCh38)
Gene constraint: LOEUF 0.585 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 73.37 · 2 PDB

Full APBB1IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APBB1IP p.Ala617Thr Benign ★★ same type
APBB1IP p.Ala622Val Benign ★★ same type
APBB1IP p.Arg429Trp Benign ★★ ⚠ same type
APBB1IP p.Phe208= Benign ★★ same type
APBB1IP p.Ala118Pro Uncertain significance ★ ⚠ same type
APBB1IP p.Ala354Val Uncertain significance ★ ⚠ same type
APBB1IP p.Ala41Thr Uncertain significance ★ ⚠ same type
APBB1IP p.Ala504Val 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/apbb1ip-p-ser438pro (accessed [today's date]).

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