Is ABCE1 p.Val105Ala (c.314T>C) pathogenic?

ABCE1 p.Val105Ala (c.314T>C) is classified Uncertain significance in ABCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.9642); Absent from gnomAD v4.1.

How common is ABCE1 p.Val105Ala (c.314T>C) in the general population?

ABCE1 p.Val105Ala (c.314T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCE1 p.Val105Ala (c.314T>C)?

AlphaMissense predicts likely pathogenic (score 0.9642) — an in-silico prediction, not a clinical call.

ABCE1 p.Val105Ala

c.314T>C · rs2546719893 · VCV2251333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9642 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9642	likely pathogenic
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -10.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 23 kb · p 3.5e-48 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ABCE1
Protein: p.Val105Ala
Coding: c.314T>C
MANE Select: NM_002940
dbSNP: rs2546719893
Type: single nucleotide variant
Location: chr4:145109158 (GRCh38)
Gene constraint: LOEUF 0.466 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.76 · 3 PDB
Residue 105: a β-strand; the abc transporter 1 domain

Full ABCE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCE1 p.Asp135Asn Uncertain significance ★★ ⚠ same type
ABCE1 p.Cys475= Benign ★★ same type
ABCE1 p.Gly110= Benign ★★ same type
ABCE1 p.Arg212Ter Uncertain significance ★ same type
ABCE1 p.Asn338His Uncertain significance ★ ⚠ same type
ABCE1 p.Asp205Gly Uncertain significance ★ ⚠ same type
ABCE1 p.Asp216Glu Uncertain significance ★ ⚠ same type
ABCE1 p.Asp3Glu 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/abce1-p-val105ala (accessed [today's date]).

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