Is AMFR p.Ala324Val (c.971C>T) pathogenic?

AMFR p.Ala324Val (c.971C>T) is classified Uncertain significance in AMFR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.2331); Absent from gnomAD v4.1.

How common is AMFR p.Ala324Val (c.971C>T) in the general population?

AMFR p.Ala324Val (c.971C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMFR p.Ala324Val (c.971C>T)?

AlphaMissense predicts likely benign (score 0.2331) — an in-silico prediction, not a clinical call.

AMFR p.Ala324Val

c.971C>T · VCV4091624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2331 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2331	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -7.31	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 20 kb · p 0.00011 · regional, not allelic
Overall
CADD	26.3	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: AMFR
Protein: p.Ala324Val
Coding: c.971C>T
MANE Select: NM_001144
Type: single nucleotide variant
Location: chr16:56402988 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.30 · 13 PDB
Residue 324: a UniProt-annotated variant site (in spg89; pathogenic)

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

Similar variants

AMFR p.Arg307Cys Uncertain significance ★★ ⚠ same type
AMFR p.Arg389His Uncertain significance ★★ ⚠ same type
AMFR c.707+1G>A Likely pathogenic ★ same type
AMFR p.Cys364Ter Pathogenic ★ same type
AMFR p.Ala231Ser Uncertain significance ★ ⚠ same type
AMFR p.Ala385Thr Uncertain significance ★ ⚠ same type
AMFR p.Ala407Pro Uncertain significance ★ ⚠ same type
AMFR p.Ala606Val 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/amfr-p-ala324val (accessed [today's date]).

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