Is ELF4 p.Asn59Lys (c.177T>A) pathogenic?

ELF4 p.Asn59Lys (c.177T>A) is classified Uncertain significance in ELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely benign (0.2432); Absent from gnomAD v4.1.

How common is ELF4 p.Asn59Lys (c.177T>A) in the general population?

ELF4 p.Asn59Lys (c.177T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELF4 p.Asn59Lys (c.177T>A)?

AlphaMissense predicts likely benign (score 0.2432) — an in-silico prediction, not a clinical call.

ELF4 p.Asn59Lys

c.177T>A · rs1232768849 · VCV2330429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2432 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2432	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -7.07	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 0.83	GERP -3.5, phastCons 0.75
Regional constraint	o/e 0.46	unconstrained · MANE · 7,223 bp · p 2.1e-06 · regional, not allelic
Overall
CADD	13.04	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELF4
Protein: p.Asn59Lys
Coding: c.177T>A
MANE Select: NM_001421
dbSNP: rs1232768849
Type: single nucleotide variant
Location: chrX:130074651 (GRCh38)
Structure: AlphaFold pLDDT 49.77

Full ELF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF4 p.Gly206Asp Uncertain significance ★★ ⚠ same type
ELF4 p.Ser413Leu Uncertain significance ★★ ⚠ same type
ELF4 p.Ala147Val Benign/Likely benign ★★ same type
ELF4 p.Arg604Cys Benign ★★ same type
ELF4 p.Ser369= Benign ★★ same type
ELF4 p.Thr503= Benign ★★ same type
ELF4 p.Arg185Ter Likely pathogenic ★ same type
ELF4 p.Arg234Ter Pathogenic ★ 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/elf4-p-asn59lys (accessed [today's date]).

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