Is DELE1 p.Pro5Ser (c.13C>T) pathogenic?

DELE1 p.Pro5Ser (c.13C>T) is classified Uncertain significance in DELE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.1055); Very rare (popmax 0.00221%, nfe).

How common is DELE1 p.Pro5Ser (c.13C>T) in the general population?

DELE1 p.Pro5Ser (c.13C>T) is very rare (popmax 0.00221%, nfe) (gnomAD).

What do computational predictors say about DELE1 p.Pro5Ser (c.13C>T)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

DELE1 p.Pro5Ser

c.13C>T · VCV4659364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -6.59	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 -0.043	GERP -5.4
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.76 · regional, not allelic
Overall
CADD	16.21	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 0.00221% European (non-Finnish) · 26/1,178,144 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00162% 26/1,609,234 alleles · very rare exomes 25/1,456,988 · genomes 1/152,246 · joint denominator

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: DELE1
Protein: p.Pro5Ser
Coding: c.13C>T
MANE Select: NM_014773
Type: single nucleotide variant
Location: chr5:141923954 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 1 PDB

Full DELE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DELE1 p.Pro5Leu Uncertain significance ★ ⚠ same residue
DELE1 p.Ala167Gly Uncertain significance ★ ⚠ same type
DELE1 p.Ala232Ser Uncertain significance ★ ⚠ same type
DELE1 p.Ala273Thr Uncertain significance ★ ⚠ same type
DELE1 p.Ala338Val Uncertain significance ★ same type
DELE1 p.Ala372Ser Uncertain significance ★ ⚠ same type
DELE1 p.Ala417Thr Uncertain significance ★ ⚠ same type
DELE1 p.Ala423Thr 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/dele1-p-pro5ser (accessed [today's date]).

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