Is AFM p.Arg155Thr (c.464G>C) pathogenic?

AFM p.Arg155Thr (c.464G>C) is classified Uncertain significance in AFM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely benign (0.1178); Absent from gnomAD v4.1.

How common is AFM p.Arg155Thr (c.464G>C) in the general population?

AFM p.Arg155Thr (c.464G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFM p.Arg155Thr (c.464G>C)?

AlphaMissense predicts likely benign (score 0.1178) — an in-silico prediction, not a clinical call.

AFM p.Arg155Thr

c.464G>C · VCV3840567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1178 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1178	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -9.29	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 0.5	GERP -2.2, phastCons 0.1
Regional constraint	o/e 1.10	unconstrained · MANE · 21 kb · p 0.0081 · regional, not allelic
Overall
CADD	3.003	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

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: AFM
Protein: p.Arg155Thr
Coding: c.464G>C
MANE Select: NM_001133
Type: single nucleotide variant
Location: chr4:73486055 (GRCh38)
Gene constraint: LOEUF 1.44 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.47 · 3 PDB
Residue 155: a disulfide bond; 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-arg155thr (accessed [today's date]).

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