Is ELF1 p.Lys465Asn (c.1395G>T) pathogenic?

ELF1 p.Lys465Asn (c.1395G>T) is classified Uncertain significance in ELF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.4344); Very rare (popmax 0.00381%, nfe).

How common is ELF1 p.Lys465Asn (c.1395G>T) in the general population?

ELF1 p.Lys465Asn (c.1395G>T) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about ELF1 p.Lys465Asn (c.1395G>T)?

AlphaMissense predicts ambiguous (score 0.4344) — an in-silico prediction, not a clinical call.

ELF1 p.Lys465Asn

c.1395G>T · rs749478443 · VCV3088231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4344 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4344	ambiguous
REVEL	0.301	indeterminate
SaProt	LLR -7.05	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.1, phastCons 0.001
Overall
CADD	17.25	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 0.00381% European (non-Finnish) · 45/1,180,050 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00291% 47/1,614,116 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,223
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,940

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.Lys465Asn
Coding: c.1395G>T
MANE Select: NM_032377 · reported on NM_172373
dbSNP: rs749478443
Type: single nucleotide variant
Location: chr13:40933890 (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.Lys465Thr Uncertain significance ★ ⚠ same residue
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

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-lys465asn (accessed [today's date]).

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