Is AFM p.Gln36Lys (c.106C>A) pathogenic?

AFM p.Gln36Lys (c.106C>A) is classified Uncertain significance in AFM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0868); Very rare (popmax 0.00679%, nfe).

How common is AFM p.Gln36Lys (c.106C>A) in the general population?

AFM p.Gln36Lys (c.106C>A) is very rare (popmax 0.00679%, nfe) (gnomAD).

What do computational predictors say about AFM p.Gln36Lys (c.106C>A)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

AFM p.Gln36Lys

c.106C>A · rs781727350 · VCV2601374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00679%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.337	indeterminate
SaProt	LLR -4.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.3	GERP 1.1, phastCons 0.026
Regional constraint	o/e 1.10	unconstrained · MANE · 21 kb · p 0.0081 · regional, not allelic
Overall
CADD	15.56	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 0.00679% European (non-Finnish) · 76/1,119,510 alleles

Filtering AF 0.00556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00508%

Overall 0.00516% 79/1,529,944 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00679%	14,730
Remaining individualsnot grpmax-eligible	0.00337%	29,681
East Asian	0.00228%	43,950

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.Gln36Lys
Coding: c.106C>A
MANE Select: NM_001133
dbSNP: rs781727350
Type: single nucleotide variant
Location: chr4:73483958 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.47 · 3 PDB
Residue 36: the albumin 1 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-gln36lys (accessed [today's date]).

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