Is EFL1 p.Pro977Ser (c.2929C>T) pathogenic?

EFL1 p.Pro977Ser (c.2929C>T) is classified Uncertain significance in EFL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-31). AlphaMissense: ambiguous (0.3672); Ultra-rare (popmax 0.0259%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EFL1 p.Pro977Ser (c.2929C>T)?

EFL1 p.Pro977Ser (c.2929C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EFL1 p.Pro977Ser (c.2929C>T) in the general population?

EFL1 p.Pro977Ser (c.2929C>T) is ultra-rare (popmax 0.0259%, nfe) (gnomAD).

What do computational predictors say about EFL1 p.Pro977Ser (c.2929C>T)?

AlphaMissense predicts ambiguous (score 0.3672) — an in-silico prediction, not a clinical call.

EFL1 p.Pro977Ser

c.2929C>T · rs201731639 · VCV1398889

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0259%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3672	ambiguous
REVEL	0.385	indeterminate
SaProt	LLR -8.76	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0014 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 0.0259% European (non-Finnish) · 306/1,180,018 alleles

Filtering AF 0.0235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0226%

Overall 0.0196% 316/1,613,960 alleles · ultra-rare exomes 296/1,461,860 · genomes 20/152,100 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0259%	3,856
Admixed American	0.00833%	12,000
Remaining individualsnot grpmax-eligible	0.008%	12,497

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.Pro977Ser
Coding: c.2929C>T
MANE Select: NM_024580
dbSNP: rs201731639
Type: single nucleotide variant
Location: chr15:82151525 (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-pro977ser (accessed [today's date]).

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