Is ELF1 p.Val451Leu (c.1351G>C) pathogenic?

ELF1 p.Val451Leu (c.1351G>C) is classified Uncertain significance in ELF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). AlphaMissense: ambiguous (0.3675); Very rare (popmax 6.84e-05%).

How common is ELF1 p.Val451Leu (c.1351G>C) in the general population?

ELF1 p.Val451Leu (c.1351G>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ELF1 p.Val451Leu (c.1351G>C)?

AlphaMissense predicts ambiguous (score 0.3675) — an in-silico prediction, not a clinical call.

ELF1 p.Val451Leu

c.1351G>C · VCV3844379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3675	ambiguous
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.10	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Overall
CADD	25.2	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

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,894 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: ELF1
Protein: p.Val451Leu
Coding: c.1351G>C
MANE Select: NM_032377 · reported on NM_172373
Type: single nucleotide variant
Location: chr13:40933934 (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-val451leu (accessed [today's date]).

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