Is DCLRE1A p.Pro166Ala (c.496C>G) pathogenic?

DCLRE1A p.Pro166Ala (c.496C>G) is classified Uncertain significance in DCLRE1A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: ambiguous (0.3763); Absent from gnomAD v4.1.

How common is DCLRE1A p.Pro166Ala (c.496C>G) in the general population?

DCLRE1A p.Pro166Ala (c.496C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCLRE1A p.Pro166Ala (c.496C>G)?

AlphaMissense predicts ambiguous (score 0.3763) — an in-silico prediction, not a clinical call.

DCLRE1A p.Pro166Ala

c.496C>G · rs957075350 · VCV2233340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3763	ambiguous
REVEL	0.832	moderately pathogenic-leaning
SaProt	LLR -4.20	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 18 kb · p 0.05 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

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: DCLRE1A
Protein: p.Pro166Ala
Coding: c.496C>G
MANE Select: NM_014881
dbSNP: rs957075350
Type: single nucleotide variant
Location: chr10:113850609 (GRCh38)
Gene constraint: LOEUF 0.856 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.30 · 318 PDB
Residue 166: the 'nuclear localization region' region

Full DCLRE1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCLRE1A p.Cys161Arg Uncertain significance ★★ ⚠ same type
DCLRE1A p.Ala178Thr Uncertain significance ★ ⚠ same type
DCLRE1A p.Ala193Val Uncertain significance ★ ⚠ same type
DCLRE1A p.Ala496Pro Uncertain significance ★ ⚠ same type
DCLRE1A p.Ala57Gly Uncertain significance ★ ⚠ same type
DCLRE1A p.Ala676Thr Uncertain significance ★ ⚠ same type
DCLRE1A p.Ala716Thr Uncertain significance ★ ⚠ same type
DCLRE1A p.Ala77Ser 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/dclre1a-p-pro166ala (accessed [today's date]).

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