Is APEX1 p.Val142= (c.426T>G) pathogenic?

APEX1 p.Val142= (c.426T>G) is classified Likely benign in APEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-16). Very rare (popmax 0.00133%, afr).

How common is APEX1 p.Val142= (c.426T>G) in the general population?

APEX1 p.Val142= (c.426T>G) is very rare (popmax 0.00133%, afr) (gnomAD).

APEX1 p.Val142=

c.426T>G · rs1594414820 · VCV748060

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.079	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.82	GERP -1.9, phastCons 0.003
Overall
CADD	7.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,946 alleles

Overall 0.000657% 1/152,242 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: APEX1
Protein: p.Val142=
Coding: c.426T>G
MANE Select: NM_001641
dbSNP: rs1594414820
Type: single nucleotide variant
Location: chr14:20456847 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.97 · 67 PDB
Residue 142: a β-strand

Full APEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APEX1 c.246+174T>C Benign ★★ same type
APEX1 c.246+189T>A Benign ★★ same type
APEX1 p.Asp148Glu Benign ★★ same type
APEX1 p.Glu101= Likely benign ★★ same type
APEX1 p.Gly241Arg Benign ★★ ⚠ same type
APEX1 p.Ile64Val Benign ★★ ⚠ same type
APEX1 p.Ala43Ser Uncertain significance ★ ⚠ same type
APEX1 p.Arg156Trp 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/apex1-p-val142 (accessed [today's date]).

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