Is DELE1 p.Pro150Ser (c.448C>T) pathogenic?

DELE1 p.Pro150Ser (c.448C>T) is classified Uncertain significance in DELE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0989); Very rare (popmax 0.0011%, sas).

How common is DELE1 p.Pro150Ser (c.448C>T) in the general population?

DELE1 p.Pro150Ser (c.448C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DELE1 p.Pro150Ser (c.448C>T)?

AlphaMissense predicts likely benign (score 0.0989) — an in-silico prediction, not a clinical call.

DELE1 p.Pro150Ser

c.448C>T · VCV4239297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0989	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.31	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 1.9	GERP 1.8, phastCons 0.52
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.76 · regional, not allelic
Overall
CADD	17.07	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 0.0011% South Asian · 1/91,078 alleles

Overall 0.000124% 2/1,614,102 alleles · very rare exomes 2/1,461,820 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	8.47e-05%	1,180,026

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: DELE1
Protein: p.Pro150Ser
Coding: c.448C>T
MANE Select: NM_014773
Type: single nucleotide variant
Location: chr5:141929617 (GRCh38)
Gene constraint: LOEUF 1.179 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 1 PDB
Residue 150: the 'disordered' region

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-pro150ser (accessed [today's date]).

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