Is DLEC1 p.Pro377Ala (c.1129C>G) pathogenic?

DLEC1 p.Pro377Ala (c.1129C>G) is classified Benign in DLEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0569); Low-frequency (popmax 4.42%, eas).

How common is DLEC1 p.Pro377Ala (c.1129C>G) in the general population?

DLEC1 p.Pro377Ala (c.1129C>G) is low-frequency (popmax 4.42%, eas) (gnomAD).

What do computational predictors say about DLEC1 p.Pro377Ala (c.1129C>G)?

AlphaMissense predicts likely benign (score 0.0569) — an in-silico prediction, not a clinical call.

DLEC1 p.Pro377Ala

c.1129C>G · rs117013868 · VCV779869

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0569 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.42%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0569	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.88	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 -0.55	GERP -3.3
Regional constraint	o/e 1.01	unconstrained · MANE · 83 kb · p 0.78 · regional, not allelic
Overall
CADD	2.747	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 4.42% East Asian · 1,980/44,800 alleles

Filtering AF 4.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.19%

Overall 0.14% 2,263/1,613,544 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	4.42%	23
Remaining individualsnot grpmax-eligible	0.342%	292
Admixed American	0.0433%	2,307
African / African-American	0.0213%	4,687
South Asian	0.0165%	6,068
European (non-Finnish)	0.00102%	98,307

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.Pro377Ala
Coding: c.1129C>G
MANE Select: NM_007335
dbSNP: rs117013868
Type: single nucleotide variant
Location: chr3:38063875 (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-pro377ala (accessed [today's date]).

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