Is DCLRE1B p.Pro482Ser (c.1444C>T) pathogenic?

DCLRE1B p.Pro482Ser (c.1444C>T) is classified Uncertain significance in DCLRE1B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0666); Rare (popmax 0.125%, afr).

How common is DCLRE1B p.Pro482Ser (c.1444C>T) in the general population?

DCLRE1B p.Pro482Ser (c.1444C>T) is rare (popmax 0.125%, afr) (gnomAD).

What do computational predictors say about DCLRE1B p.Pro482Ser (c.1444C>T)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

DCLRE1B p.Pro482Ser

c.1444C>T · rs201447479 · VCV2407351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.88	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 -0.061	GERP -0.82
Regional constraint	o/e 0.93	unconstrained · MANE · 1,003 bp · p 0.13 · regional, not allelic
Overall
CADD	8.237	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 0.125% African / African-American · 94/75,052 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0971%

Overall 0.00595% 96/1,614,184 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.125%	798
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	8.47e-05%	1,180,030

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: DCLRE1B
Protein: p.Pro482Ser
Coding: c.1444C>T
MANE Select: NM_022836
dbSNP: rs201447479
Type: single nucleotide variant
Location: chr1:113912036 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 74.95 · 5 PDB
Residue 482: a UniProt-annotated variant site (in dkcb8); the 'disordered' region

Full DCLRE1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCLRE1B p.Ala383Val Uncertain significance ★★ ⚠ same type
DCLRE1B p.Arg283His Uncertain significance ★★ ⚠ same type
DCLRE1B p.Arg46Leu Uncertain significance ★★ ⚠ same type
DCLRE1B p.Arg46Trp Uncertain significance ★★ ⚠ same type
DCLRE1B p.Asp308Gly Uncertain significance ★★ ⚠ same type
DCLRE1B p.Cys149Trp Uncertain significance ★★ ⚠ same type
DCLRE1B p.Gln293His Uncertain significance ★★ ⚠ same type
DCLRE1B p.Gln388Arg 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/dclre1b-p-pro482ser (accessed [today's date]).

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