Is EFL1 p.Pro159Ser (c.475C>T) pathogenic?

EFL1 p.Pro159Ser (c.475C>T) is classified Uncertain significance in EFL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: likely benign (0.134); Absent from gnomAD v4.1.

How common is EFL1 p.Pro159Ser (c.475C>T) in the general population?

EFL1 p.Pro159Ser (c.475C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EFL1 p.Pro159Ser (c.475C>T)?

AlphaMissense predicts likely benign (score 0.134) — an in-silico prediction, not a clinical call.

EFL1 p.Pro159Ser

c.475C>T · VCV3653529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.134 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.134	likely benign
REVEL	0.447	indeterminate
SaProt	LLR -11.22	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 15 kb · p 0.89 · regional, not allelic
Overall
CADD	22.2	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: EFL1
Protein: p.Pro159Ser
Coding: c.475C>T
MANE Select: NM_024580
Type: single nucleotide variant
Location: chr15:82240459 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 2 PDB
Residue 159: the tr-type g domain

Full EFL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFL1 c.1444+3A>C Uncertain significance ★★ same type
EFL1 c.244+2T>G Uncertain significance ★★ same type
EFL1 p.Ala755Thr Uncertain significance ★★ ⚠ same type
EFL1 p.Arg108His Uncertain significance ★★ ⚠ same type
EFL1 p.Arg1097Trp Uncertain significance ★★ ⚠ same type
EFL1 p.Arg330Trp Uncertain significance ★★ ⚠ same type
EFL1 p.Arg444His Uncertain significance ★★ ⚠ same type
EFL1 p.Arg970Cys 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/efl1-p-pro159ser (accessed [today's date]).

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