Is EFTUD2 p.Phe770Ser (c.2309T>C) pathogenic?

EFTUD2 p.Phe770Ser (c.2309T>C) is classified Likely pathogenic in EFTUD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-21). AlphaMissense: likely pathogenic (0.9987); Absent from gnomAD v4.1; Associated with mandibulofacial dysostosis-microcephaly syndrome.

What condition is associated with EFTUD2 p.Phe770Ser (c.2309T>C)?

EFTUD2 p.Phe770Ser (c.2309T>C) is associated with mandibulofacial dysostosis-microcephaly syndrome (ClinVar).

How common is EFTUD2 p.Phe770Ser (c.2309T>C) in the general population?

EFTUD2 p.Phe770Ser (c.2309T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFTUD2 p.Phe770Ser (c.2309T>C)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

EFTUD2 p.Phe770Ser

c.2309T>C · rs2508728187 · VCV2671921

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mandibulofacial dysostosis-microcephaly syndrome

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic ✓ concordant with ClinVar · top 4% in EFTUD2
REVEL	0.748	pathogenic-leaning
SaProt	LLR -15.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 5,858 bp · p 6.8e-32 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EFTUD2
Protein: p.Phe770Ser
Coding: c.2309T>C
MANE Select: NM_004247
dbSNP: rs2508728187
Type: single nucleotide variant
Location: chr17:44854307 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.94 · 72 PDB
Residue 770: an α-helix

Full EFTUD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mandibulofacial dysostosis-microcephaly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFTUD2 c.1058+1G>A Pathogenic ★★ same condition
EFTUD2 c.1414-2A>G Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 c.1607+1G>T Likely pathogenic ★★ same condition
EFTUD2 c.2133-2A>G Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 c.2562-2A>G Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 c.703-2A>G Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 p.Arg262Trp Pathogenic ★★ same condition
EFTUD2 p.Arg354Ter Pathogenic/Likely pathogenic ★★ 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/eftud2-p-phe770ser (accessed [today's date]).

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