Is EEF1D p.Arg336= (c.1008G>T) pathogenic?

EEF1D p.Arg336= (c.1008G>T) is classified Benign in EEF1D (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-24). Common (popmax 85.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with EEF1D-related disorder.

What condition is associated with EEF1D p.Arg336= (c.1008G>T)?

EEF1D p.Arg336= (c.1008G>T) is associated with EEF1D-related disorder (ClinVar).

EEF1D p.Arg336=

Q: How common is EEF1D p.Arg336= (c.1008G>T) in the general population?

EEF1D p.Arg336= (c.1008G>T) is common (popmax 85.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1008G>T · rs4874160 · VCV3060921

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 85.6%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

EEF1D-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.005	GERP -2.5
Overall
CADD	1.733	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 85.6% European (non-Finnish) · 1,009,519/1,179,272 alleles

Filtering AF 85.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 85.4%

Overall 81.3% 1,307,804/1,608,322 alleles · common exomes 1,196,510/1,456,168 · genomes 111,294/152,154 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	85.6%	1
Finnishnot grpmax-eligible	82.8%	1
Ashkenazi Jewishnot grpmax-eligible	82.3%	1
Middle Eastern	82.2%	1
Amishnot grpmax-eligible	82%	1
Remaining individualsnot grpmax-eligible	80%	1
Admixed American	72.1%	1
South Asian	70.3%	1
East Asian	51.9%	2
African / African-American	51.5%	2

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: EEF1D
Protein: p.Arg336=
Coding: c.1008G>T
MANE Select: NM_001130053
dbSNP: rs4874160
Type: single nucleotide variant
Location: chr8:143589074 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 4 PDB
Residue 336: a UniProt-annotated variant site (in nedtchal; likely pathogenic)

Full EEF1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EEF1D-related disorder

Similar variants

EEF1D p.Arg336Gln Uncertain significance ★ same residue
EEF1D p.Arg336Trp Uncertain significance ★ same residue
EEF1D p.Asp386Asn Uncertain significance ★★ ⚠ same condition
EEF1D p.Arg292Ter Likely pathogenic ★ same condition
EEF1D p.Gln610Ter Likely pathogenic ★ same condition
EEF1D c.1288-10T>C Likely benign same condition
EEF1D p.Ala35= Likely benign same condition
EEF1D p.Ala549Ser Likely benign same condition

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/eef1d-p-arg336 (accessed [today's date]).

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