Is ATP4B p.Phe142Val (c.424T>G) pathogenic?

ATP4B p.Phe142Val (c.424T>G) is classified Uncertain significance in ATP4B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). AlphaMissense: likely pathogenic (0.7053); Ultra-rare (popmax 0.0164%, mid).

How common is ATP4B p.Phe142Val (c.424T>G) in the general population?

ATP4B p.Phe142Val (c.424T>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ATP4B p.Phe142Val (c.424T>G)?

AlphaMissense predicts likely pathogenic (score 0.7053) — an in-silico prediction, not a clinical call.

ATP4B p.Phe142Val

c.424T>G · rs748237973 · VCV2544527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7053	likely pathogenic
REVEL	0.198	benign-leaning
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,767 bp · p 0.62 · regional, not allelic
Overall
CADD	19.82	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,613,998 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00203%	49,167
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: ATP4B
Protein: p.Phe142Val
Coding: c.424T>G
MANE Select: NM_000705
dbSNP: rs748237973
Type: single nucleotide variant
Location: chr13:113653004 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.68
Residue 142: a disulfide bond

Full ATP4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP4B p.Ala166Glu Uncertain significance ★ ⚠ same type
ATP4B p.Ala260Thr Uncertain significance ★ ⚠ same type
ATP4B p.Ala2Val Uncertain significance ★ ⚠ same type
ATP4B p.Arg13Cys Uncertain significance ★ ⚠ same type
ATP4B p.Arg13Ser Uncertain significance ★ ⚠ same type
ATP4B p.Arg143Cys Uncertain significance ★ ⚠ same type
ATP4B p.Arg143His Uncertain significance ★ ⚠ same type
ATP4B p.Arg208His 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/atp4b-p-phe142val (accessed [today's date]).

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