Is ENOSF1 p.Ser193Leu (c.578C>T) pathogenic?

ENOSF1 p.Ser193Leu (c.578C>T) is classified Uncertain significance in ENOSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: ambiguous (0.561); Very rare (popmax 0.00267%, afr).

How common is ENOSF1 p.Ser193Leu (c.578C>T) in the general population?

ENOSF1 p.Ser193Leu (c.578C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ENOSF1 p.Ser193Leu (c.578C>T)?

AlphaMissense predicts ambiguous (score 0.561) — an in-silico prediction, not a clinical call.

ENOSF1 p.Ser193Leu

c.578C>T · rs780093389 · VCV2333563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.561 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.561	ambiguous
REVEL	0.493	indeterminate
SaProt	LLR -9.77	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 38 kb · p 0.14 · regional, not allelic
Overall
CADD	25.7	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 0.00267% African / African-American · 2/74,896 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00124% 20/1,613,862 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,448
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00136%	73,752
South Asian	0.0011%	91,084

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: ENOSF1
Protein: p.Ser193Leu
Coding: c.578C>T
MANE Select: NM_017512
dbSNP: rs780093389
Type: single nucleotide variant
Location: chr18:690589 (GRCh38)
Gene constraint: LOEUF 1.236 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.47 · 1 PDB

Full ENOSF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENOSF1 c.*1219T>C Benign ★★ same type
TYMS c.556+1G>A Pathogenic ★ same type
TYMS p.Arg271Ter Pathogenic ★ same type
ENOSF1 c.84+108G>C Uncertain significance ★ same type
ENOSF1 c.84+112A>C Uncertain significance ★ same type
ENOSF1 c.84+114C>G Uncertain significance ★ same type
ENOSF1 c.84+125T>C Uncertain significance ★ same type
ENOSF1 c.84+130A>C 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/enosf1-p-ser193leu (accessed [today's date]).

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