Is ELF3 p.Cys5Arg (c.13T>C) pathogenic?

ELF3 p.Cys5Arg (c.13T>C) is classified Uncertain significance in ELF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely pathogenic (0.6147); Ultra-rare (popmax 0.0508%, nfe).

How common is ELF3 p.Cys5Arg (c.13T>C) in the general population?

ELF3 p.Cys5Arg (c.13T>C) is ultra-rare (popmax 0.0508%, nfe) (gnomAD).

What do computational predictors say about ELF3 p.Cys5Arg (c.13T>C)?

AlphaMissense predicts likely pathogenic (score 0.6147) — an in-silico prediction, not a clinical call.

ELF3 p.Cys5Arg

c.13T>C · rs143610955 · VCV3088240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6147 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0508%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6147	likely pathogenic
REVEL	0.269	benign-leaning
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,697 bp · p 0.032 · regional, not allelic
Overall
CADD	26.2	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 0.0508% European (non-Finnish) · 599/1,179,972 alleles

Filtering AF 0.0474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.046%

Overall 0.0403% 651/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0508%	1,970
Admixed American	0.0417%	2,400
Remaining individualsnot grpmax-eligible	0.024%	4,167
African / African-American	0.0133%	7,505
Finnishnot grpmax-eligible	0.00312%	32,014

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.Cys5Arg
Coding: c.13T>C
MANE Select: NM_004433
dbSNP: rs143610955
Type: single nucleotide variant
Location: chr1:202011149 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.32 · 1 PDB

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-cys5arg (accessed [today's date]).

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