Is AVIL p.Leu747Phe (c.2239C>T) pathogenic?

AVIL p.Leu747Phe (c.2239C>T) is classified Likely benign in AVIL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-20). AlphaMissense: likely benign (0.0633); Rare (popmax 0.128%, afr); Associated with AVIL-related disorder.

What condition is associated with AVIL p.Leu747Phe (c.2239C>T)?

AVIL p.Leu747Phe (c.2239C>T) is associated with AVIL-related disorder (ClinVar).

How common is AVIL p.Leu747Phe (c.2239C>T) in the general population?

AVIL p.Leu747Phe (c.2239C>T) is rare (popmax 0.128%, afr) (gnomAD).

What do computational predictors say about AVIL p.Leu747Phe (c.2239C>T)?

AlphaMissense predicts likely benign (score 0.0633) — an in-silico prediction, not a clinical call.

AVIL p.Leu747Phe

c.2239C>T · rs79289432 · VCV3054986

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0633 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.128%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AVIL-related disorder

Computational evidence

Protein change
AlphaMissense	0.0633	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -8.84	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 0.1	GERP -2.8, phastCons 0.61
Regional constraint	o/e 0.88	unconstrained · MANE · 18 kb · p 9.4e-05 · regional, not allelic
Overall
CADD	14.44	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

Grpmax group 0.128% African / African-American · 96/75,042 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0995%

Overall 0.00712% 115/1,614,164 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.128%	782
Admixed American	0.0183%	5,456
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	8.47e-05%	1,180,032

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: AVIL
Protein: p.Leu747Phe
Coding: c.2239C>T
MANE Select: NM_006576
dbSNP: rs79289432
Type: single nucleotide variant
Location: chr12:57799902 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 747: the 'headpiece' region; the 'required for interaction with f-actin' region

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

Disease context

AVIL-related disorder

Similar variants

AVIL p.Leu747Arg Uncertain significance ★ ⚠ same residue
AVIL p.Glu667Lys Uncertain significance ⚠ same condition
AVIL c.1818-6T>C Likely benign same condition
AVIL p.Gln413= Likely benign same condition
AVIL p.Gly299Arg Likely benign ⚠ same condition
AVIL p.Gly434= Likely benign same condition
AVIL p.Leu679= Likely benign same condition
AVIL p.Leu764= Likely benign same condition

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-leu747phe (accessed [today's date]).

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