Is AVIL p.Ile316Phe (c.946A>T) pathogenic?

AVIL p.Ile316Phe (c.946A>T) is classified Uncertain significance in AVIL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: ambiguous (0.5006); Absent from gnomAD v4.1.

How common is AVIL p.Ile316Phe (c.946A>T) in the general population?

AVIL p.Ile316Phe (c.946A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVIL p.Ile316Phe (c.946A>T)?

AlphaMissense predicts ambiguous (score 0.5006) — an in-silico prediction, not a clinical call.

AVIL p.Ile316Phe

c.946A>T · rs2540999226 · VCV2604478

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5006 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5006	ambiguous
REVEL	0.256	benign-leaning
SaProt	LLR -14.17	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 18 kb · p 9.4e-05 · regional, not allelic
Overall
CADD	25.1	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: AVIL
Protein: p.Ile316Phe
Coding: c.946A>T
MANE Select: NM_006576
dbSNP: rs2540999226
Type: single nucleotide variant
Location: chr12:57808542 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 316: the 'core' region

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

Similar variants

AVIL p.Arg199Ter Likely pathogenic ★★ same type
AVIL p.Asn777Lys Uncertain significance ★★ ⚠ same type
AVIL p.Gly577Ser Uncertain significance ★★ ⚠ same type
AVIL p.Gly626Ser Uncertain significance ★★ ⚠ same type
AVIL p.Ile250Thr Uncertain significance ★★ ⚠ same type
AVIL c.1194+202C>T Benign ★★ same type
AVIL c.2151+142A>G Benign ★★ same type
AVIL c.67-155C>T Benign ★★ 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/avil-p-ile316phe (accessed [today's date]).

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