Is DLEU7 p.Ser129Leu (c.386C>T) pathogenic?

DLEU7 p.Ser129Leu (c.386C>T) is classified Uncertain significance in DLEU7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.3282); Ultra-rare (popmax 0.0119%, eas).

How common is DLEU7 p.Ser129Leu (c.386C>T) in the general population?

DLEU7 p.Ser129Leu (c.386C>T) is ultra-rare (popmax 0.0119%, eas) (gnomAD).

What do computational predictors say about DLEU7 p.Ser129Leu (c.386C>T)?

AlphaMissense predicts likely benign (score 0.3282) — an in-silico prediction, not a clinical call.

DLEU7 p.Ser129Leu

c.386C>T · rs375022108 · VCV2466657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3282 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3282	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.54	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 4.3	GERP 4.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.7 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0119% East Asian · 5/42,102 alleles

Filtering AF 0.00468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00301%

Overall 0.000565% 9/1,592,446 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0119%	8,420
Remaining individualsnot grpmax-eligible	0.00325%	30,737
South Asian	0.00111%	89,892
European (non-Finnish)	8.55e-05%	1,169,665

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: DLEU7
Protein: p.Ser129Leu
Coding: c.386C>T
MANE Select: NM_001306135
dbSNP: rs375022108
Type: single nucleotide variant
Location: chr13:50843261 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.45

Full DLEU7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLEU7 p.Ala2Val Uncertain significance ★ ⚠ same type
DLEU7 p.Ala49Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala51Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala80Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala83Pro Uncertain significance ★ ⚠ same type
DLEU7 p.Ala9Ser Uncertain significance ★ ⚠ same type
DLEU7 p.Arg123Gly Uncertain significance ★ ⚠ same type
DLEU7 p.Arg52Ser 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/dleu7-p-ser129leu (accessed [today's date]).

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