Is DLEC1 p.Thr413Met (c.1238C>T) pathogenic?

DLEC1 p.Thr413Met (c.1238C>T) is classified Uncertain significance in DLEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). AlphaMissense: likely benign (0.1796); Ultra-rare (popmax 0.0165%, mid).

How common is DLEC1 p.Thr413Met (c.1238C>T) in the general population?

DLEC1 p.Thr413Met (c.1238C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DLEC1 p.Thr413Met (c.1238C>T)?

AlphaMissense predicts likely benign (score 0.1796) — an in-silico prediction, not a clinical call.

DLEC1 p.Thr413Met

c.1238C>T · rs777349201 · VCV3082704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1796	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -12.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 83 kb · p 0.78 · regional, not allelic
Overall
CADD	25.7	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 0.0165% Middle Eastern · 1/6,066 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0134%

Overall 0.0134% 216/1,612,506 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,066
European (non-Finnish)	0.016%	6,239
African / African-American	0.0134%	7,463
Remaining individualsnot grpmax-eligible	0.0112%	8,912
East Asian	0.00669%	14,953
South Asian	0.00329%	30,360
Finnishnot grpmax-eligible	0.00313%	31,953
Admixed American	0.00167%	59,932

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: DLEC1
Protein: p.Thr413Met
Coding: c.1238C>T
MANE Select: NM_007335
dbSNP: rs777349201
Type: single nucleotide variant
Location: chr3:38084222 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.51

Full DLEC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLEC1 p.Ala727= Benign ★★ same type
DLEC1 p.Asn885= Benign ★★ same type
DLEC1 p.Leu1219= Likely benign ★★ same type
DLEC1 p.Leu1672= Benign ★★ same type
DLEC1 p.Leu871= Benign/Likely benign ★★ same type
DLEC1 p.Lys1022Asn Benign ★★ same type
DLEC1 p.Ser1268= Benign ★★ same type
DLEC1 p.Ser181= Benign ★★ 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/dlec1-p-thr413met (accessed [today's date]).

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