Is EEF1D p.Pro398Ser (c.1192C>T) pathogenic?

EEF1D p.Pro398Ser (c.1192C>T) is classified Uncertain significance in EEF1D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.1234); Ultra-rare (popmax 0.0121%, sas).

How common is EEF1D p.Pro398Ser (c.1192C>T) in the general population?

EEF1D p.Pro398Ser (c.1192C>T) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about EEF1D p.Pro398Ser (c.1192C>T)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

EEF1D p.Pro398Ser

c.1192C>T · VCV3506763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 10 kb · p 0.79 · regional, not allelic
Overall
CADD	23.5	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P32S vs ClinVar P398S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,088 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.000682% 11/1,613,964 alleles · ultra-rare exomes 11/1,461,568 · genomes 0/152,396 · joint denominator

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.Pro398Ser
Coding: c.1192C>T
MANE Select: NM_001130053
Type: single nucleotide variant
Location: chr8:143586752 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 4 PDB

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

Similar variants

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
EEF1D p.Thr575Met 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-pro398ser (accessed [today's date]).

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