Is AFM p.Gln211Arg (c.632A>G) pathogenic?

AFM p.Gln211Arg (c.632A>G) is classified Uncertain significance in AFM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-02). AlphaMissense: likely benign (0.0786); Very rare (popmax 0.00314%, nfe).

How common is AFM p.Gln211Arg (c.632A>G) in the general population?

AFM p.Gln211Arg (c.632A>G) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about AFM p.Gln211Arg (c.632A>G)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

AFM p.Gln211Arg

c.632A>G · rs765287577 · VCV2521088

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.06
Regional constraint	o/e 1.10	unconstrained · MANE · 21 kb · p 0.0081 · regional, not allelic
Overall
CADD	13.98	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

Grpmax group 0.00314% European (non-Finnish) · 37/1,178,458 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00242% 39/1,611,948 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,850
Admixed American	0.00167%	59,898
Remaining individualsnot grpmax-eligible	0.0016%	62,412

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.Gln211Arg
Coding: c.632A>G
MANE Select: NM_001133
dbSNP: rs765287577
Type: single nucleotide variant
Location: chr4:73487740 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.47 · 3 PDB
Residue 211: 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.Gln211Lys Uncertain significance ★ ⚠ same residue
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

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-gln211arg (accessed [today's date]).

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