Is APPBP2 p.Val571Leu (c.1711G>C) pathogenic?

APPBP2 p.Val571Leu (c.1711G>C) is classified Uncertain significance in APPBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.3399); Very rare (popmax 0.000508%, nfe).

How common is APPBP2 p.Val571Leu (c.1711G>C) in the general population?

APPBP2 p.Val571Leu (c.1711G>C) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about APPBP2 p.Val571Leu (c.1711G>C)?

AlphaMissense predicts likely benign (score 0.3399) — an in-silico prediction, not a clinical call.

APPBP2 p.Val571Leu

c.1711G>C · rs1360592487 · VCV2623019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3399 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3399	likely benign
REVEL	0.377	indeterminate
SaProt	LLR -5.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 189 bp · p 0.019 · regional, not allelic
Overall
CADD	22.5	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 0.000508% European (non-Finnish) · 6/1,180,018 alleles

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

Overall 0.000372% 6/1,613,942 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: APPBP2
Protein: p.Val571Leu
Coding: c.1711G>C
MANE Select: NM_006380
dbSNP: rs1360592487
Type: single nucleotide variant
Location: chr17:60447628 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.52 · 6 PDB
Residue 571: an α-helix

Full APPBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APPBP2 p.Ala272Gly Uncertain significance ★ ⚠ same type
APPBP2 p.Arg161Cys Uncertain significance ★ ⚠ same type
APPBP2 p.Arg27His Uncertain significance ★ ⚠ same type
APPBP2 p.Arg545Gln Uncertain significance ★ ⚠ same type
APPBP2 p.Arg71Thr Uncertain significance ★ ⚠ same type
APPBP2 p.Asn24Ser Uncertain significance ★ ⚠ same type
APPBP2 p.Asp154Asn Uncertain significance ★ ⚠ same type
APPBP2 p.Gln487His 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/appbp2-p-val571leu (accessed [today's date]).

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