Is EEF1D p.Ala549Ser (c.1645G>T) pathogenic?

EEF1D p.Ala549Ser (c.1645G>T) is classified Likely benign in EEF1D (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-21). AlphaMissense: likely benign (0.1008); Rare (popmax 0.318%, afr); Associated with EEF1D-related disorder.

What condition is associated with EEF1D p.Ala549Ser (c.1645G>T)?

EEF1D p.Ala549Ser (c.1645G>T) is associated with EEF1D-related disorder (ClinVar).

How common is EEF1D p.Ala549Ser (c.1645G>T) in the general population?

EEF1D p.Ala549Ser (c.1645G>T) is rare (popmax 0.318%, afr) (gnomAD).

What do computational predictors say about EEF1D p.Ala549Ser (c.1645G>T)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

EEF1D p.Ala549Ser

c.1645G>T · rs142439099 · VCV3049853

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.318%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EEF1D-related disorder

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -7.73	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 -1.3, phastCons 0.99
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.79 · regional, not allelic
Overall
CADD	22.8	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 A183S vs ClinVar A549S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.318% African / African-American · 239/75,058 alleles

Filtering AF 0.285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.272%

Overall 0.0167% 269/1,613,390 alleles · rare exomes 122/1,461,024 · genomes 147/152,366 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.318%	314
Remaining individualsnot grpmax-eligible	0.0288%	3,471
Admixed American	0.02%	5,002

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.Ala549Ser
Coding: c.1645G>T
MANE Select: NM_001130053
dbSNP: rs142439099
Type: single nucleotide variant
Location: chr8:143580571 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 4 PDB
Residue 183 UniProt numbering: an α-helix; the 'catalytic (gef)' region

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

Disease context

EEF1D-related disorder

Similar variants

EEF1D p.Ala549Thr 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.Ala578= Benign same condition
EEF1D p.Arg110= 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-ala549ser (accessed [today's date]).

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