Is ELF2 p.Thr461Ile (c.1382C>T) pathogenic?

ELF2 p.Thr461Ile (c.1382C>T) is classified Uncertain significance in ELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.9054); Absent from gnomAD v4.1.

How common is ELF2 p.Thr461Ile (c.1382C>T) in the general population?

ELF2 p.Thr461Ile (c.1382C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELF2 p.Thr461Ile (c.1382C>T)?

AlphaMissense predicts likely pathogenic (score 0.9054) — an in-silico prediction, not a clinical call.

ELF2 p.Thr461Ile

c.1382C>T · VCV4248196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9054 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9054	likely pathogenic
REVEL	0.158	moderately benign-leaning
SaProt	LLR -9.28	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,626 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	25.3	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

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: ELF2
Protein: p.Thr461Ile
Coding: c.1382C>T
MANE Select: NM_001331036
Type: single nucleotide variant
Location: chr4:139059383 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.58 · 1 PDB

Full ELF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF2 p.Ala4Thr Likely pathogenic ★ ⚠ same type
ELF2 p.Ala135Pro Uncertain significance ★ ⚠ same type
ELF2 p.Ala368Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala383Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala428Val Uncertain significance ★ ⚠ same type
ELF2 p.Ala444Gly Uncertain significance ★ ⚠ same type
ELF2 p.Ala517Ser Uncertain significance ★ ⚠ same type
ELF2 p.Ala541Thr 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/elf2-p-thr461ile (accessed [today's date]).

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