Is DLEC1 p.Ser85Phe (c.254C>T) pathogenic?

DLEC1 p.Ser85Phe (c.254C>T) is classified Uncertain significance in DLEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: ambiguous (0.3432); Very rare (popmax 0.00492%, nfe).

How common is DLEC1 p.Ser85Phe (c.254C>T) in the general population?

DLEC1 p.Ser85Phe (c.254C>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about DLEC1 p.Ser85Phe (c.254C>T)?

AlphaMissense predicts ambiguous (score 0.3432) — an in-silico prediction, not a clinical call.

DLEC1 p.Ser85Phe

c.254C>T · VCV3502282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3432	ambiguous
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.80	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.9, phastCons 0.73
Regional constraint	o/e 1.01	unconstrained · MANE · 83 kb · p 0.78 · regional, not allelic
Overall
CADD	27.0	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 0.00492% European (non-Finnish) · 58/1,179,898 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00372% 60/1,613,934 alleles · very rare exomes 56/1,461,646 · genomes 4/152,288 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,343
Remaining individualsnot grpmax-eligible	0.0032%	31,233

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.Ser85Phe
Coding: c.254C>T
MANE Select: NM_007335
Type: single nucleotide variant
Location: chr3:38039479 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.51

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-ser85phe (accessed [today's date]).

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