Is AARD p.Phe6Leu (c.18C>A) pathogenic?

AARD p.Phe6Leu (c.18C>A) is classified Uncertain significance in AARD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-01). AlphaMissense: likely pathogenic (0.5993); Absent from gnomAD v4.1.

How common is AARD p.Phe6Leu (c.18C>A) in the general population?

AARD p.Phe6Leu (c.18C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AARD p.Phe6Leu (c.18C>A)?

AlphaMissense predicts likely pathogenic (score 0.5993) — an in-silico prediction, not a clinical call.

AARD p.Phe6Leu

c.18C>A · VCV3261441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5993	likely pathogenic · top 3% in AARD
REVEL	0.06	moderately benign-leaning
SaProt	LLR -4.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -1.9
Regional constraint	o/e 1.12	unconstrained · MANE · 4,454 bp · p 0.076 · regional, not allelic
Overall
CADD	1.81	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

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: AARD
Protein: p.Phe6Leu
Coding: c.18C>A
MANE Select: NM_001025357
Type: single nucleotide variant
Location: chr8:116938261 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.24

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

Similar variants

AARD p.Ala70= Benign ★★ same type
AARD p.Ala82Thr Uncertain significance ★ ⚠ same type
AARD p.Ala82Val Uncertain significance ★ ⚠ same type
AARD p.Ala83Gly Uncertain significance ★ ⚠ same type
AARD p.Ala85Gly Uncertain significance ★ ⚠ same type
AARD p.Arg103Thr Uncertain significance ★ ⚠ same type
AARD p.Asp150Glu Uncertain significance ★ ⚠ same type
AARD p.Gln130Lys 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/aard-p-phe6leu (accessed [today's date]).

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