Is AP4B1 p.Val640Phe (c.1918G>T) pathogenic?

AP4B1 p.Val640Phe (c.1918G>T) is classified Uncertain significance in AP4B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). AlphaMissense: likely benign (0.1583); Absent from gnomAD v4.1.

How common is AP4B1 p.Val640Phe (c.1918G>T) in the general population?

AP4B1 p.Val640Phe (c.1918G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP4B1 p.Val640Phe (c.1918G>T)?

AlphaMissense predicts likely benign (score 0.1583) — an in-silico prediction, not a clinical call.

AP4B1 p.Val640Phe

c.1918G>T · rs2526482684 · VCV2639003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1583 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1583	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -12.17	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 4	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 9,649 bp · p 0.84 · regional, not allelic
Overall
CADD	22.2	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

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: AP4B1
Protein: p.Val640Phe
Coding: c.1918G>T
MANE Select: NM_001253852
dbSNP: rs2526482684
Type: single nucleotide variant
Location: chr1:113895367 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.56 · 5 PDB
Residue 640: the 'ear; mediates interaction with tepsin' region

Full AP4B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP4B1 p.Val640Gly Uncertain significance ★★ ⚠ same residue
AP4B1 c.114-2A>C Pathogenic ★★ same type
AP4B1 c.114-2A>G Pathogenic ★★ same type
AP4B1 p.Arg102Ter Pathogenic ★★ same type
AP4B1 p.Arg206Ter Pathogenic/Likely pathogenic ★★ same type
AP4B1 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same type
AP4B1 p.Arg393Ter Pathogenic ★★ same type
AP4B1 p.Arg406Ter Pathogenic/Likely pathogenic ★★ 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/ap4b1-p-val640phe (accessed [today's date]).

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