Is ELF3 p.Arg205Trp (c.613C>T) pathogenic?

ELF3 p.Arg205Trp (c.613C>T) is classified Uncertain significance in ELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely benign (0.0733); Very rare (popmax 0.00483%, nfe).

How common is ELF3 p.Arg205Trp (c.613C>T) in the general population?

ELF3 p.Arg205Trp (c.613C>T) is very rare (popmax 0.00483%, nfe) (gnomAD).

What do computational predictors say about ELF3 p.Arg205Trp (c.613C>T)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

ELF3 p.Arg205Trp

c.613C>T · VCV3507855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 0.85, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,697 bp · p 0.032 · regional, not allelic
Overall
CADD	22.2	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 0.00483% European (non-Finnish) · 57/1,179,136 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00391% 63/1,612,264 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,687
Admixed American	0.00334%	29,898
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,420
African / African-American	0.00134%	74,876
South Asian	0.0011%	90,728

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: ELF3
Protein: p.Arg205Trp
Coding: c.613C>T
MANE Select: NM_004433
Type: single nucleotide variant
Location: chr1:202012961 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.32 · 1 PDB
Residue 205: the 'disordered' region

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

Similar variants

ELF3 p.Asn104= Benign ★★ 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
ELF3 p.Asp96Glu 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-arg205trp (accessed [today's date]).

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