Is AFM p.Arg360Gly (c.1078A>G) pathogenic?

AFM p.Arg360Gly (c.1078A>G) is classified Uncertain significance in AFM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: ambiguous (0.5481); Ultra-rare (popmax 0.0998%, mid).

How common is AFM p.Arg360Gly (c.1078A>G) in the general population?

AFM p.Arg360Gly (c.1078A>G) is ultra-rare (popmax 0.0998%, mid) (gnomAD).

What do computational predictors say about AFM p.Arg360Gly (c.1078A>G)?

AlphaMissense predicts ambiguous (score 0.5481) — an in-silico prediction, not a clinical call.

AFM p.Arg360Gly

c.1078A>G · rs200798387 · VCV2344128

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5481 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0998%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5481	ambiguous
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -11.50	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 21 kb · p 0.0081 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.0998% Middle Eastern · 6/6,012 alleles

Filtering AF 0.0458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.0102% 163/1,593,278 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0998%	1,002
South Asian	0.0586%	1,706
Remaining individualsnot grpmax-eligible	0.0162%	6,167
European (non-Finnish)	0.00758%	13,201
African / African-American	0.0041%	24,410
Admixed American	0.00382%	26,187
Ashkenazi Jewishnot grpmax-eligible	0.00348%	28,702
Finnishnot grpmax-eligible	0.00157%	63,782

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: AFM
Protein: p.Arg360Gly
Coding: c.1078A>G
MANE Select: NM_001133
dbSNP: rs200798387
Type: single nucleotide variant
Location: chr4:73495319 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.47 · 3 PDB
Residue 360: a disulfide bond; the albumin 2 domain; an α-helix

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

Similar variants

AFM p.Ala100Val Uncertain significance ★ ⚠ same type
AFM p.Ala150Pro Uncertain significance ★ ⚠ same type
AFM p.Ala241Val Uncertain significance ★ ⚠ same type
AFM p.Ala352Glu Uncertain significance ★ ⚠ same type
AFM p.Ala352Val Uncertain significance ★ ⚠ same type
AFM p.Ala397Thr Uncertain significance ★ ⚠ same type
AFM p.Ala397Val Uncertain significance ★ ⚠ same type
AFM p.Ala439Pro 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/afm-p-arg360gly (accessed [today's date]).

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