Is ELF3 p.Thr54Lys (c.161C>A) pathogenic?

ELF3 p.Thr54Lys (c.161C>A) is classified Uncertain significance in ELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.12); Absent from gnomAD v4.1.

How common is ELF3 p.Thr54Lys (c.161C>A) in the general population?

ELF3 p.Thr54Lys (c.161C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELF3 p.Thr54Lys (c.161C>A)?

AlphaMissense predicts likely benign (score 0.12) — an in-silico prediction, not a clinical call.

ELF3 p.Thr54Lys

c.161C>A · rs2102991403 · VCV2548975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.12 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.12	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -5.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Constraint at this position
Conservation	phyloP 3.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,697 bp · p 0.032 · regional, not allelic
Overall
CADD	26.4	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: ELF3
Protein: p.Thr54Lys
Coding: c.161C>A
MANE Select: NM_004433
dbSNP: rs2102991403
Type: single nucleotide variant
Location: chr1:202011297 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.32 · 1 PDB
Residue 54: the pnt domain

Full ELF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELF3 p.Asn104= Benign ★★ same type
ELF3 p.Arg205Trp Uncertain significance ★ ⚠ same type
ELF3 p.Arg233Cys Uncertain significance ★ ⚠ same type
ELF3 p.Arg307His Uncertain significance ★ ⚠ same type
ELF3 p.Arg370Gln Uncertain significance ★ ⚠ same type
ELF3 p.Arg370Trp Uncertain significance ★ ⚠ same type
ELF3 p.Asp220Tyr Uncertain significance ★ ⚠ same type
ELF3 p.Asp234Asn 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/elf3-p-thr54lys (accessed [today's date]).

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