Is DLEC1 p.Pro1525Ser (c.4573C>T) pathogenic?

DLEC1 p.Pro1525Ser (c.4573C>T) is classified Uncertain significance in DLEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely pathogenic (0.8076); Very rare (popmax 0.00223%, eas).

How common is DLEC1 p.Pro1525Ser (c.4573C>T) in the general population?

DLEC1 p.Pro1525Ser (c.4573C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DLEC1 p.Pro1525Ser (c.4573C>T)?

AlphaMissense predicts likely pathogenic (score 0.8076) — an in-silico prediction, not a clinical call.

DLEC1 p.Pro1525Ser

c.4573C>T · VCV4011975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8076 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8076	likely pathogenic · top 8% in DLEC1
REVEL	0.274	benign-leaning
SaProt	LLR -6.77	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.39	acceptor gain · deltas
Pangolin	Δ0.30	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 83 kb · p 0.78 · regional, not allelic
Overall
CADD	28.7	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 0.00223% East Asian · 1/44,876 alleles

Overall 0.000137% 2/1,461,868 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
Admixed American	0.00167%	60,026

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.Pro1525Ser
Coding: c.4573C>T
MANE Select: NM_007335
Type: single nucleotide variant
Location: chr3:38117893 (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-pro1525ser (accessed [today's date]).

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