Is ELF1 p.Pro589Leu (c.1766C>T) pathogenic?

ELF1 p.Pro589Leu (c.1766C>T) is classified Uncertain significance in ELF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.0706); Very rare (popmax 0.00729%, nfe).

How common is ELF1 p.Pro589Leu (c.1766C>T) in the general population?

ELF1 p.Pro589Leu (c.1766C>T) is very rare (popmax 0.00729%, nfe) (gnomAD).

What do computational predictors say about ELF1 p.Pro589Leu (c.1766C>T)?

AlphaMissense predicts likely benign (score 0.0706) — an in-silico prediction, not a clinical call.

ELF1 p.Pro589Leu

c.1766C>T · rs368677066 · VCV3088233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0706	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.20	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 5.2	GERP 1.9, phastCons 0.99
Overall
CADD	16.78	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 0.00729% European (non-Finnish) · 86/1,180,046 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00539% 87/1,614,080 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,721
African / African-American	0.00133%	74,922

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: ELF1
Protein: p.Pro589Leu
Coding: c.1766C>T
MANE Select: NM_032377 · reported on NM_172373
dbSNP: rs368677066
Type: single nucleotide variant
Location: chr13:40933519 (GRCh38)
Structure: AlphaFold pLDDT 85.98 · 7 PDB

Full ELF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF1 p.Leu614= Benign ★★ same type
ELF1 p.Pro364= Benign ★★ same type
ELF1 p.Ala29Thr Uncertain significance ★ ⚠ same type
ELF1 p.Ala353Ser Uncertain significance ★ ⚠ same type
ELF1 p.Ala459Val Uncertain significance ★ ⚠ same type
ELF1 p.Arg323Thr Uncertain significance ★ ⚠ same type
ELF1 p.Arg328Gln Uncertain significance ★ ⚠ same type
ELF1 p.Arg330Lys 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/elf1-p-pro589leu (accessed [today's date]).

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