Is AVEN p.Trp82Cys (c.246G>T) pathogenic?

AVEN p.Trp82Cys (c.246G>T) is classified Uncertain significance in AVEN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: ambiguous (0.4044); Rare (popmax 0.96%, afr).

How common is AVEN p.Trp82Cys (c.246G>T) in the general population?

AVEN p.Trp82Cys (c.246G>T) is rare (popmax 0.96%, afr) (gnomAD).

What do computational predictors say about AVEN p.Trp82Cys (c.246G>T)?

AlphaMissense predicts ambiguous (score 0.4044) — an in-silico prediction, not a clinical call.

AVEN p.Trp82Cys

c.246G>T · VCV4186041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4044 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.96%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4044	ambiguous
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.96	GERP -0.004
Regional constraint	o/e 1.38	unconstrained · MANE · 172 kb · p 2.1e-15 · regional, not allelic
Overall
CADD	14.93	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 0.96% African / African-American · 590/61,488 alleles

Filtering AF 0.895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.87%

Overall 0.053% 633/1,193,284 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.96%	104
Admixed American	0.0654%	1,528
Remaining individualsnot grpmax-eligible	0.0504%	1,984
South Asian	0.0034%	29,448
European (non-Finnish)	0.000519%	192,521

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: AVEN
Protein: p.Trp82Cys
Coding: c.246G>T
MANE Select: NM_020371
Type: single nucleotide variant
Location: chr15:34038801 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.86
Residue 82: the 'disordered' region

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

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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/aven-p-trp82cys (accessed [today's date]).

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