Is DLEC1 p.Ser192Phe (c.575C>T) pathogenic?

DLEC1 p.Ser192Phe (c.575C>T) is classified Benign in DLEC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-03). AlphaMissense: likely benign (0.0398); Low-frequency (popmax 4.35%, afr).

How common is DLEC1 p.Ser192Phe (c.575C>T) in the general population?

DLEC1 p.Ser192Phe (c.575C>T) is low-frequency (popmax 4.35%, afr) (gnomAD).

What do computational predictors say about DLEC1 p.Ser192Phe (c.575C>T)?

AlphaMissense predicts likely benign (score 0.0398) — an in-silico prediction, not a clinical call.

DLEC1 p.Ser192Phe

c.575C>T · rs34012183 · VCV769271

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0398 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.35%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0398	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -4.89	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 4.8	GERP 0.94, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 83 kb · p 0.78 · regional, not allelic
Overall
CADD	14.6	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 4.35% African / African-American · 3,262/75,010 alleles

Filtering AF 4.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.17%

Overall 0.258% 4,158/1,613,884 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.35%	23
Middle Eastern	0.445%	225
Remaining individualsnot grpmax-eligible	0.44%	227
Admixed American	0.427%	234
European (non-Finnish)	0.0273%	3,664
South Asian	0.0165%	6,070
East Asian	0.00223%	44,880

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: DLEC1
Protein: p.Ser192Phe
Coding: c.575C>T
MANE Select: NM_007335
dbSNP: rs34012183
Type: single nucleotide variant
Location: chr3:38059754 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.51
Residue 192: a UniProt-annotated variant site (in)

Full DLEC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLEC1 p.Ala727= Benign ★★ same type
DLEC1 p.Asn885= Benign ★★ same type
DLEC1 p.Leu1219= Likely benign ★★ same type
DLEC1 p.Leu1672= Benign ★★ same type
DLEC1 p.Leu871= Benign/Likely benign ★★ same type
DLEC1 p.Lys1022Asn Benign ★★ same type
DLEC1 p.Ser1268= Benign ★★ same type
DLEC1 p.Ser181= Benign ★★ 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/dlec1-p-ser192phe (accessed [today's date]).

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