Is ELF4 p.Arg329Gln (c.986G>A) pathogenic?

ELF4 p.Arg329Gln (c.986G>A) is classified Uncertain significance in ELF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-07). AlphaMissense: likely benign (0.1124); Very rare (popmax 0.00435%, amr).

How common is ELF4 p.Arg329Gln (c.986G>A) in the general population?

ELF4 p.Arg329Gln (c.986G>A) is very rare (popmax 0.00435%, amr) (gnomAD).

What do computational predictors say about ELF4 p.Arg329Gln (c.986G>A)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

ELF4 p.Arg329Gln

c.986G>A · rs745964330 · VCV3088247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00435%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.06	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 2.6	GERP 0.69, phastCons 0.98
Regional constraint	o/e 0.97	unconstrained · MANE · 2,786 bp · p 0.57 · regional, not allelic
Overall
CADD	20.6	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 0.00435% Admixed American · 2/45,999 alleles

Filtering AF 0.000721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00027%

Overall 0.000826% 10/1,211,287 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00435%	23,000
African / African-American	0.00173%	57,644
European (non-Finnish)	0.000782%	127,922

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: ELF4
Protein: p.Arg329Gln
Coding: c.986G>A
MANE Select: NM_001421
dbSNP: rs745964330
Type: single nucleotide variant
Location: chrX:130069501 (GRCh38)
Structure: AlphaFold pLDDT 49.77
Residue 329: the 'disordered' region

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

Similar variants

ELF4 p.Arg329Ter Pathogenic ★ same residue
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

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-arg329gln (accessed [today's date]).

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