Is AVIL p.Ser501Phe (c.1502C>T) pathogenic?

AVIL p.Ser501Phe (c.1502C>T) is classified Uncertain significance in AVIL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.675); Ultra-rare (popmax 0.0209%, sas).

How common is AVIL p.Ser501Phe (c.1502C>T) in the general population?

AVIL p.Ser501Phe (c.1502C>T) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

What do computational predictors say about AVIL p.Ser501Phe (c.1502C>T)?

AlphaMissense predicts likely pathogenic (score 0.675) — an in-silico prediction, not a clinical call.

AVIL p.Ser501Phe

c.1502C>T · rs755293608 · VCV2209623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.675 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.675	likely pathogenic
REVEL	0.473	indeterminate
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 18 kb · p 9.4e-05 · regional, not allelic
Overall
CADD	29.5	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 0.0209% South Asian · 19/91,086 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00143% 23/1,613,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,794
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	8.47e-05%	1,180,008

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.Ser501Phe
Coding: c.1502C>T
MANE Select: NM_006576
dbSNP: rs755293608
Type: single nucleotide variant
Location: chr12:57806529 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 1 PDB
Residue 501: 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-ser501phe (accessed [today's date]).

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