Is ALCAM p.Asp386Val (c.1157A>T) pathogenic?

ALCAM p.Asp386Val (c.1157A>T) is classified Uncertain significance in ALCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely pathogenic (0.9739); Absent from gnomAD v4.1.

How common is ALCAM p.Asp386Val (c.1157A>T) in the general population?

ALCAM p.Asp386Val (c.1157A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALCAM p.Asp386Val (c.1157A>T)?

AlphaMissense predicts likely pathogenic (score 0.9739) — an in-silico prediction, not a clinical call.

ALCAM p.Asp386Val

c.1157A>T · VCV3519570

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9739 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9739	likely pathogenic · top 8% in ALCAM
REVEL	0.557	indeterminate
SaProt	LLR -13.27	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ALCAM
Protein: p.Asp386Val
Coding: c.1157A>T
MANE Select: NM_001627
Type: single nucleotide variant
Location: chr3:105547201 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 1 PDB
Residue 386: a disulfide bond; the ig-like c2-type 2 domain

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

Similar variants

ALCAM p.Asp81= Benign ★★ same type
ALCAM p.His508= Benign/Likely benign ★★ same type
ALCAM p.Leu254= Benign ★★ same type
ALCAM p.Pro84Leu Benign ★★ ⚠ same type
ALCAM p.Ser454= Benign/Likely benign ★★ same type
ALCAM p.Thr301Met Benign ★★ ⚠ same type
ALCAM p.Tyr224= Benign ★★ same type
ALCAM p.Ala19Pro 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/alcam-p-asp386val (accessed [today's date]).

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