Is ALCAM p.Arg360Ser (c.1080G>T) pathogenic?

ALCAM p.Arg360Ser (c.1080G>T) is classified Benign in ALCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-20). AlphaMissense: ambiguous (0.3832); Rare (popmax 0.515%, nfe).

How common is ALCAM p.Arg360Ser (c.1080G>T) in the general population?

ALCAM p.Arg360Ser (c.1080G>T) is rare (popmax 0.515%, nfe) (gnomAD).

What do computational predictors say about ALCAM p.Arg360Ser (c.1080G>T)?

AlphaMissense predicts ambiguous (score 0.3832) — an in-silico prediction, not a clinical call.

ALCAM p.Arg360Ser

c.1080G>T · rs139344282 · VCV774843

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3832 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.515%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3832	ambiguous
REVEL	0.44	indeterminate
SaProt	LLR -5.14	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.14, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 180 kb · p 0.27 · regional, not allelic
Overall
CADD	17.31	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

Grpmax group 0.515% European (non-Finnish) · 6,051/1,175,462 alleles

Filtering AF 0.504% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.499%

Overall 0.433% 6,968/1,607,990 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.05%	95
European (non-Finnish)grpmax	0.515%	194
Remaining individualsnot grpmax-eligible	0.225%	444
African / African-American	0.075%	1,334
South Asian	0.0352%	2,843
Admixed American	0.0184%	5,432
Middle Eastern	0.0166%	6,020
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,340

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ALCAM
Protein: p.Arg360Ser
Coding: c.1080G>T
MANE Select: NM_001627
dbSNP: rs139344282
Type: single nucleotide variant
Location: chr3:105545311 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 1 PDB
Residue 360: 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-arg360ser (accessed [today's date]).

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