Is CD46 p.Asp257Val (c.770A>T) pathogenic?

CD46 p.Asp257Val (c.770A>T) is classified Uncertain significance in CD46 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-03). AlphaMissense: likely benign (0.2073); Absent from gnomAD v4.1.

How common is CD46 p.Asp257Val (c.770A>T) in the general population?

CD46 p.Asp257Val (c.770A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD46 p.Asp257Val (c.770A>T)?

AlphaMissense predicts likely benign (score 0.2073) — an in-silico prediction, not a clinical call.

CD46 p.Asp257Val

c.770A>T · VCV3713894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2073 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2073	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -8.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Regional constraint	o/e 0.88	unconstrained · MANE · 38 kb · p 0.012 · regional, not allelic
Overall
CADD	0.051	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

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: CD46
Protein: p.Asp257Val
Coding: c.770A>T
MANE Select: NM_172351
Type: single nucleotide variant
Location: chr1:207767109 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 82.38 · 7 PDB
Residue 257: a disulfide bond; the sushi 4 domain

Full CD46 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD46 p.Asp257Asn Uncertain significance ★ ⚠ same residue
CD46 p.Asp257fs Pathogenic ★ same residue
CD46 c.1082+2T>A Pathogenic ★★ same type
CD46 c.286+1G>C Pathogenic/Likely pathogenic ★★ same type
CD46 c.286+2T>G Pathogenic/Likely pathogenic ★★ same type
CD46 c.287-2A>G Pathogenic/Likely pathogenic ★★ same type
CD46 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same type
CD46 p.Arg59Ter Pathogenic/Likely pathogenic ★★ 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/cd46-p-asp257val (accessed [today's date]).

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