Is DLEC1 p.Phe1644Cys (c.4931T>G) pathogenic?

DLEC1 p.Phe1644Cys (c.4931T>G) is classified Uncertain significance in DLEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely pathogenic (0.9076); Absent from gnomAD v4.1.

How common is DLEC1 p.Phe1644Cys (c.4931T>G) in the general population?

DLEC1 p.Phe1644Cys (c.4931T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLEC1 p.Phe1644Cys (c.4931T>G)?

AlphaMissense predicts likely pathogenic (score 0.9076) — an in-silico prediction, not a clinical call.

DLEC1 p.Phe1644Cys

c.4931T>G · rs2471534447 · VCV3082737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9076 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9076	likely pathogenic · top 4% in DLEC1
REVEL	0.668	pathogenic-leaning
SaProt	LLR -12.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DLEC1
Protein: p.Phe1644Cys
Coding: c.4931T>G
MANE Select: NM_007335
dbSNP: rs2471534447
Type: single nucleotide variant
Location: chr3:38121692 (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-phe1644cys (accessed [today's date]).

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