Is NT5E p.Ala114= (c.342A>G) pathogenic?

NT5E p.Ala114= (c.342A>G) is classified Benign in NT5E (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Common (popmax 6.6%, afr) — too common for a highly-penetrant pathogenic allele.

NT5E p.Ala114=

Q: How common is NT5E p.Ala114= (c.342A>G) in the general population?

NT5E p.Ala114= (c.342A>G) is common (popmax 6.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.342A>G · rs35694460 · VCV783471

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6.6%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP -1.5, phastCons 0.85
Overall
CADD	10.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.6% African / African-American · 4,947/74,978 alleles

Filtering AF 6.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.38%

Overall 0.347% 5,607/1,613,664 alleles · common exomes 2,754/1,461,442 · genomes 2,853/152,222 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.6%	15
Admixed American	0.467%	214
Remaining individualsnot grpmax-eligible	0.451%	222
Middle Eastern	0.314%	319
South Asian	0.0165%	6,071
European (non-Finnish)	0.00543%	18,432

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: NT5E
Protein: p.Ala114=
Coding: c.342A>G
MANE Select: NM_002526
dbSNP: rs35694460
Type: single nucleotide variant
Location: chr6:85467062 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.95 · 52 PDB
Residue 114: a β-strand

Full NT5E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NT5E c.1210+12G>C Benign ★★ same type
NT5E p.Gly148= Likely benign ★★ same type
NT5E p.Thr376Ala Benign ★★ same type
NT5E p.Thr407= Benign/Likely benign ★★ same type
NT5E c.1104+2T>A Likely pathogenic ★ same type
NT5E p.Cys476Ter Likely pathogenic ★ same type
NT5E c.562+1G>T Uncertain significance ★ same type
NT5E p.Ala10Pro 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/nt5e-p-ala114 (accessed [today's date]).

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