Is AVEN p.Thr272Ser (c.814A>T) pathogenic?

AVEN p.Thr272Ser (c.814A>T) is classified Uncertain significance in AVEN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1.

How common is AVEN p.Thr272Ser (c.814A>T) in the general population?

AVEN p.Thr272Ser (c.814A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVEN p.Thr272Ser (c.814A>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

AVEN p.Thr272Ser

c.814A>T · VCV3812586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.39	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -4.1	GERP -3.5
Regional constraint	o/e 1.38	unconstrained · MANE · 172 kb · p 2.1e-15 · regional, not allelic
Overall
CADD	1.199	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: AVEN
Protein: p.Thr272Ser
Coding: c.814A>T
MANE Select: NM_020371
Type: single nucleotide variant
Location: chr15:33867654 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.86
Residue 272: the 'disordered' region

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

Similar variants

RYR3 p.Ala4568Pro Uncertain significance ★★ ⚠ same type
RYR3 p.Ala4594Val Uncertain significance ★★ ⚠ same type
RYR3 p.Ala4650Thr Uncertain significance ★★ ⚠ same type
RYR3 p.Arg4862His Uncertain significance ★★ ⚠ same type
RYR3 p.Glu4573Gln Uncertain significance ★★ same type
RYR3 p.His4609Arg Uncertain significance ★★ ⚠ same type
RYR3 p.Ile4604Thr Uncertain significance ★★ ⚠ same type
RYR3 p.Lys4579Arg Uncertain significance ★★ 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/aven-p-thr272ser (accessed [today's date]).

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