Is EFL1 p.Ser504Phe (c.1511C>T) pathogenic?

EFL1 p.Ser504Phe (c.1511C>T) is classified Conflicting classifications of pathogenicity in EFL1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0908); Rare (popmax 0.155%, afr); Associated with Inborn genetic diseases.

What condition is associated with EFL1 p.Ser504Phe (c.1511C>T)?

EFL1 p.Ser504Phe (c.1511C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EFL1 p.Ser504Phe (c.1511C>T) in the general population?

EFL1 p.Ser504Phe (c.1511C>T) is rare (popmax 0.155%, afr) (gnomAD).

What do computational predictors say about EFL1 p.Ser504Phe (c.1511C>T)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

EFL1 p.Ser504Phe

c.1511C>T · rs376776701 · VCV1434240

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.155%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -7.15	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 5	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 5,409 bp · p 0.064 · regional, not allelic
Overall
CADD	18.41	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 0.155% African / African-American · 116/74,994 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00861% 139/1,613,994 alleles · rare exomes 67/1,461,762 · genomes 72/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.155%	647
Admixed American	0.02%	5,001
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.000169%	589,977

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: EFL1
Protein: p.Ser504Phe
Coding: c.1511C>T
MANE Select: NM_024580
dbSNP: rs376776701
Type: single nucleotide variant
Location: chr15:82219752 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFL1 c.1444+3A>C Uncertain significance ★★ same condition
EFL1 p.Arg970Cys Uncertain significance ★★ ⚠ same condition
EFL1 p.Asp317Gly Uncertain significance ★★ ⚠ same condition
EFL1 p.Gln172Arg Uncertain significance ★★ ⚠ same condition
EFL1 p.Gly1078Glu Uncertain significance ★★ ⚠ same condition
EFL1 p.Ile301Leu Uncertain significance ★★ ⚠ same condition
EFL1 p.Met984Val Uncertain significance ★★ ⚠ same condition
EFL1 p.Pro492Ser Uncertain significance ★★ ⚠ 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/efl1-p-ser504phe (accessed [today's date]).

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