Is ELF2 p.Thr514Ile (c.1541C>T) pathogenic?

ELF2 p.Thr514Ile (c.1541C>T) is classified Uncertain significance in ELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: likely benign (0.1366); Very rare (popmax 8.48e-05%, nfe).

How common is ELF2 p.Thr514Ile (c.1541C>T) in the general population?

ELF2 p.Thr514Ile (c.1541C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ELF2 p.Thr514Ile (c.1541C>T)?

AlphaMissense predicts likely benign (score 0.1366) — an in-silico prediction, not a clinical call.

ELF2 p.Thr514Ile

c.1541C>T · rs769494640 · VCV2489496

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1366 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1366	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	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	22.7	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,878 alleles

Overall 0.000657% 1/152,192 alleles · very rare

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: ELF2
Protein: p.Thr514Ile
Coding: c.1541C>T
MANE Select: NM_001331036
dbSNP: rs769494640
Type: single nucleotide variant
Location: chr4:139059224 (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-thr514ile (accessed [today's date]).

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