Is EEF1D p.Arg489Trp (c.1465C>T) pathogenic?

EEF1D p.Arg489Trp (c.1465C>T) is classified Uncertain significance in EEF1D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). AlphaMissense: likely benign (0.0973); Ultra-rare (popmax 0.0201%, eas).

How common is EEF1D p.Arg489Trp (c.1465C>T) in the general population?

EEF1D p.Arg489Trp (c.1465C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about EEF1D p.Arg489Trp (c.1465C>T)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

EEF1D p.Arg489Trp

c.1465C>T · rs200186152 · VCV3087271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.79 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R123W vs ClinVar R489W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,874 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.0036% 58/1,612,188 alleles · ultra-rare exomes 39/1,459,834 · genomes 19/152,354 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
Middle Eastern	0.0189%	5,296
Admixed American	0.0183%	5,457
Remaining individualsnot grpmax-eligible	0.0144%	6,933
African / African-American	0.00666%	15,007
South Asian	0.0033%	30,345
European (non-Finnish)	0.00169%	58,998

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.Arg489Trp
Coding: c.1465C>T
MANE Select: NM_001130053
dbSNP: rs200186152
Type: single nucleotide variant
Location: chr8:143581077 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 4 PDB
Residue 123 UniProt numbering: the 'disordered' region

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

Similar variants

EEF1D p.Arg489Gln Uncertain significance ★ ⚠ same residue
EEF1D c.1905+1G>A Uncertain significance ★★ same type
EEF1D p.Arg585Cys Uncertain significance ★★ ⚠ same type
EEF1D p.Asp100Gly Uncertain significance ★★ same type
EEF1D p.Asp386Asn Uncertain significance ★★ ⚠ same type
EEF1D p.Gly351Ala Uncertain significance ★★ same type
EEF1D p.Pro350Leu Uncertain significance ★★ same type
EEF1D p.Ser213Asn 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/eef1d-p-arg489trp (accessed [today's date]).

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