Is EFL1 p.Ser781Phe (c.2342C>T) pathogenic?

EFL1 p.Ser781Phe (c.2342C>T) is classified Benign/Likely benign in EFL1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.0989); Rare (popmax 0.773%, afr).

How common is EFL1 p.Ser781Phe (c.2342C>T) in the general population?

EFL1 p.Ser781Phe (c.2342C>T) is rare (popmax 0.773%, afr) (gnomAD).

What do computational predictors say about EFL1 p.Ser781Phe (c.2342C>T)?

AlphaMissense predicts likely benign (score 0.0989) — an in-silico prediction, not a clinical call.

EFL1 p.Ser781Phe

c.2342C>T · rs115354615 · VCV720725

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0989 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.773%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0989	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0014 · regional, not allelic
Overall
CADD	20.2	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

Grpmax group 0.773% African / African-American · 580/75,026 alleles

Filtering AF 0.721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.7%

Overall 0.0412% 665/1,614,090 alleles · rare exomes 320/1,461,852 · genomes 345/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.773%	129
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Admixed American	0.0533%	1,875
European (non-Finnish)	0.000932%	107,275

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.Ser781Phe
Coding: c.2342C>T
MANE Select: NM_024580
dbSNP: rs115354615
Type: single nucleotide variant
Location: chr15:82152112 (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

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-ser781phe (accessed [today's date]).

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