Is DELE1 p.Pro13Ser (c.37C>T) pathogenic?

DELE1 p.Pro13Ser (c.37C>T) is classified Uncertain significance in DELE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.1106); Ultra-rare (popmax 0.0627%, sas).

How common is DELE1 p.Pro13Ser (c.37C>T) in the general population?

DELE1 p.Pro13Ser (c.37C>T) is ultra-rare (popmax 0.0627%, sas) (gnomAD).

What do computational predictors say about DELE1 p.Pro13Ser (c.37C>T)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

DELE1 p.Pro13Ser

c.37C>T · rs369129396 · VCV3081387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0627%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.77	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 2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.76 · regional, not allelic
Overall
CADD	17.97	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 0.0627% South Asian · 57/90,918 alleles

Filtering AF 0.0497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.045%

Overall 0.00996% 160/1,606,310 alleles · ultra-rare exomes 144/1,454,162 · genomes 16/152,148 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0627%	1,595
Middle Eastern	0.0494%	2,026
Finnishnot grpmax-eligible	0.025%	4,002
Admixed American	0.02%	5,000
Remaining individualsnot grpmax-eligible	0.0193%	5,184
European (non-Finnish)	0.00477%	20,946
African / African-American	0.00401%	24,918
East Asian	0.00223%	44,848

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.Pro13Ser
Coding: c.37C>T
MANE Select: NM_014773
dbSNP: rs369129396
Type: single nucleotide variant
Location: chr5:141924586 (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.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
DELE1 p.Ala423Val 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-pro13ser (accessed [today's date]).

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