Is EFL1 p.Phe505Ser (c.1514T>C) pathogenic?

EFL1 p.Phe505Ser (c.1514T>C) is classified Likely pathogenic in EFL1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-10). AlphaMissense: likely pathogenic (0.8873); Very rare (popmax 0.00667%, afr); Associated with Shwachman-Diamond syndrome.

What condition is associated with EFL1 p.Phe505Ser (c.1514T>C)?

EFL1 p.Phe505Ser (c.1514T>C) is associated with Shwachman-Diamond syndrome, Shwachman-Diamond syndrome 2 (ClinVar).

How common is EFL1 p.Phe505Ser (c.1514T>C) in the general population?

EFL1 p.Phe505Ser (c.1514T>C) is very rare (popmax 0.00667%, afr) (gnomAD).

How is Shwachman-Diamond syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EFL1 p.Phe505Ser (c.1514T>C)?

AlphaMissense predicts likely pathogenic (score 0.8873) — an in-silico prediction, not a clinical call.

EFL1 p.Phe505Ser

c.1514T>C · rs763132789 · VCV1686815

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Shwachman-Diamond syndrome

Computational evidence

Protein change
AlphaMissense	0.8873	likely pathogenic ✓ concordant with ClinVar
REVEL	0.602	indeterminate
SaProt	LLR -14.12	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 5,409 bp · p 0.064 · regional, not allelic
Overall
CADD	27.7	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 0.00667% African / African-American · 5/74,914 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00118% 19/1,613,956 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,983
South Asian	0.00439%	22,771
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000678%	147,495

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.Phe505Ser
Coding: c.1514T>C
MANE Select: NM_024580
dbSNP: rs763132789
Type: single nucleotide variant
Location: chr15:82219749 (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

Shwachman-Diamond syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Shwachman-Diamond syndrome 2

For Shwachman-Diamond syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Italy)

Similar variants

EFL1 p.Arg1097Trp Uncertain significance ★★ ⚠ same condition
EFL1 p.Arg970Cys Uncertain significance ★★ ⚠ same condition
EFL1 p.Arg970His Uncertain significance ★★ ⚠ same condition
EFL1 p.Gly850Ser Uncertain significance ★★ ⚠ same condition
EFL1 p.His449Tyr Uncertain significance ★★ ⚠ same condition
EFL1 p.Ile411Asn Uncertain significance ★★ ⚠ same condition
EFL1 p.Ile742Val Uncertain significance ★★ ⚠ same condition
EFL1 p.Leu263Val 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-phe505ser (accessed [today's date]).

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