Is APBB1IP p.Ala41Thr (c.121G>A) pathogenic?

APBB1IP p.Ala41Thr (c.121G>A) is classified Uncertain significance in APBB1IP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.0651); Very rare (popmax 0.00167%, amr).

How common is APBB1IP p.Ala41Thr (c.121G>A) in the general population?

APBB1IP p.Ala41Thr (c.121G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about APBB1IP p.Ala41Thr (c.121G>A)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

APBB1IP p.Ala41Thr

c.121G>A · rs2494639979 · VCV2232159

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.66	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 1.8	GERP -2.9, phastCons 0.004
Regional constraint	o/e 0.95	unconstrained · MANE · 49 kb · p 0.35 · regional, not allelic
Overall
CADD	11.81	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 0.00167% Admixed American · 1/59,956 alleles

Overall 0.000137% 2/1,460,782 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,956
South Asian	0.0011%	91,024

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.Ala41Thr
Coding: c.121G>A
MANE Select: NM_019043
dbSNP: rs2494639979
Type: single nucleotide variant
Location: chr10:26496352 (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.Ala504Val Uncertain significance ★ ⚠ same type
APBB1IP p.Ala609Val 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-ala41thr (accessed [today's date]).

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