Is DNER p.Thr142Ile (c.425C>T) pathogenic?

DNER p.Thr142Ile (c.425C>T) is classified Benign in DNER (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-26). AlphaMissense: likely benign (0.1102); Low-frequency (popmax 3.33%, afr).

How common is DNER p.Thr142Ile (c.425C>T) in the general population?

DNER p.Thr142Ile (c.425C>T) is low-frequency (popmax 3.33%, afr) (gnomAD).

What do computational predictors say about DNER p.Thr142Ile (c.425C>T)?

AlphaMissense predicts likely benign (score 0.1102) — an in-silico prediction, not a clinical call.

DNER p.Thr142Ile

c.425C>T · rs147533391 · VCV716097

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1102 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.33%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1102	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 356 kb · p 0.066 · regional, not allelic
Overall
CADD	21.1	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 3.33% African / African-American · 2,500/75,044 alleles

Filtering AF 3.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.18%

Overall 0.177% 2,863/1,614,210 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.33%	30
Admixed American	0.29%	345
Remaining individualsnot grpmax-eligible	0.259%	386
Middle Eastern	0.066%	1,516
South Asian	0.00988%	10,120
European (non-Finnish)	0.00119%	84,288

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: DNER
Protein: p.Thr142Ile
Coding: c.425C>T
MANE Select: NM_139072
dbSNP: rs147533391
Type: single nucleotide variant
Location: chr2:229591740 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 70.51

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

Similar variants

DNER p.Thr142Ser Likely benign ★ same residue
DNER c.586-10C>T Benign ★★ same type
DNER p.Arg698= Benign ★★ same type
DNER p.Pro180= Benign ★★ same type
DNER p.Ala11Val Uncertain significance ★ ⚠ same type
DNER p.Ala171Thr Uncertain significance ★ ⚠ same type
DNER p.Ala205Thr Uncertain significance ★ ⚠ same type
DNER p.Ala234Thr 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/dner-p-thr142ile (accessed [today's date]).

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