Is AVIL p.Pro322Ser (c.964C>T) pathogenic?

AVIL p.Pro322Ser (c.964C>T) is classified Benign in AVIL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1013); Low-frequency (popmax 1.15%, afr).

How common is AVIL p.Pro322Ser (c.964C>T) in the general population?

AVIL p.Pro322Ser (c.964C>T) is low-frequency (popmax 1.15%, afr) (gnomAD).

What do computational predictors say about AVIL p.Pro322Ser (c.964C>T)?

AlphaMissense predicts likely benign (score 0.1013) — an in-silico prediction, not a clinical call.

AVIL p.Pro322Ser

c.964C>T · rs147969047 · VCV722301

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1013 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1013	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -9.31	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 2.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 18 kb · p 9.4e-05 · regional, not allelic
Overall
CADD	21.1	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

Grpmax group 1.15% African / African-American · 860/75,010 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.0623% 1,005/1,614,060 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.15%	87
Admixed American	0.123%	811
Remaining individualsnot grpmax-eligible	0.0928%	1,078
South Asian	0.00439%	22,767
European (non-Finnish)	0.000763%	131,111

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.Pro322Ser
Coding: c.964C>T
MANE Select: NM_006576
dbSNP: rs147969047
Type: single nucleotide variant
Location: chr12:57808524 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 322: 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-pro322ser (accessed [today's date]).

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