Is EEF1A2 p.Ser175Asn (c.524G>A) pathogenic?

EEF1A2 p.Ser175Asn (c.524G>A) is classified Likely benign in EEF1A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-08). AlphaMissense: ambiguous (0.4535); Very rare (popmax 6.85e-05%).

How common is EEF1A2 p.Ser175Asn (c.524G>A) in the general population?

EEF1A2 p.Ser175Asn (c.524G>A) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about EEF1A2 p.Ser175Asn (c.524G>A)?

AlphaMissense predicts ambiguous (score 0.4535) — an in-silico prediction, not a clinical call.

EEF1A2 p.Ser175Asn

c.524G>A · rs2145944783 · VCV1202499

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4535 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4535	ambiguous
REVEL	0.143	moderately benign-leaning
SaProt	LLR -12.96	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 1,861 bp · p 1.2e-12 · regional, not allelic
Overall
CADD	27.4	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 6.85e-05%

Overall 6.85e-05% 1/1,460,456 alleles · very rare

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: EEF1A2
Protein: p.Ser175Asn
Coding: c.524G>A
MANE Select: NM_001958
dbSNP: rs2145944783
Type: single nucleotide variant
Location: chr20:63494902 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 2 PDB
Residue 175: the tr-type g domain; an α-helix

Full EEF1A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEF1A2 p.Ser175= Likely benign ★★ same residue
EEF1A2 p.Ser175Lys Uncertain significance ★ same residue
EEF1A2 p.Arg266Gln Likely pathogenic ★★ same type
EEF1A2 p.Arg266Trp Pathogenic/Likely pathogenic ★★ same type
EEF1A2 p.Arg423Cys Pathogenic/Likely pathogenic ★★ same type
EEF1A2 p.Arg69Cys Pathogenic ★★ same type
EEF1A2 p.Asp252Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
EEF1A2 p.Asp91Asn 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/eef1a2-p-ser175asn (accessed [today's date]).

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