Is ELF2 p.Thr440Pro (c.1318A>C) pathogenic?

ELF2 p.Thr440Pro (c.1318A>C) is classified Uncertain significance in ELF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). AlphaMissense: likely benign (0.1971); Very rare (popmax 0.00167%, amr).

How common is ELF2 p.Thr440Pro (c.1318A>C) in the general population?

ELF2 p.Thr440Pro (c.1318A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ELF2 p.Thr440Pro (c.1318A>C)?

AlphaMissense predicts likely benign (score 0.1971) — an in-silico prediction, not a clinical call.

ELF2 p.Thr440Pro

c.1318A>C · rs1727487692 · VCV2340370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1971	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -8.51	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 5	GERP 0.92, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,626 bp · p 8.7e-05 · regional, not allelic
Overall
CADD	25.0	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 0.00167% Admixed American · 1/60,016 alleles

Overall 0.000137% 2/1,461,664 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,016
European (non-Finnish)	8.48e-05%	1,179,860

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.Thr440Pro
Coding: c.1318A>C
MANE Select: NM_001331036
dbSNP: rs1727487692
Type: single nucleotide variant
Location: chr4:139059447 (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.Thr440Ile Uncertain significance ★ same residue
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

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-thr440pro (accessed [today's date]).

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