Is DAZL p.Pro221Leu (c.662C>T) pathogenic?

DAZL p.Pro221Leu (c.662C>T) is classified Uncertain significance in DAZL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.0739); Absent from gnomAD v4.1.

How common is DAZL p.Pro221Leu (c.662C>T) in the general population?

DAZL p.Pro221Leu (c.662C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAZL p.Pro221Leu (c.662C>T)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

DAZL p.Pro221Leu

c.662C>T · rs2546471751 · VCV2543260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 0.96, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 8,330 bp · p 0.48 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAZL
Protein: p.Pro221Leu
Coding: c.662C>T
MANE Select: NM_001351
dbSNP: rs2546471751
Type: single nucleotide variant
Location: chr3:16593728 (GRCh38)
Gene constraint: LOEUF 0.2 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.38

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

Similar variants

DAZL p.Arg201Lys Uncertain significance ★ ⚠ same type
DAZL p.Arg250Gln Uncertain significance ★ ⚠ same type
DAZL p.Arg62Lys Uncertain significance ★ ⚠ same type
DAZL p.Asn102His Uncertain significance ★ ⚠ same type
DAZL p.Asn10His Uncertain significance ★ ⚠ same type
DAZL p.Asn132Ser Uncertain significance ★ ⚠ same type
DAZL p.Asn145Lys Uncertain significance ★ ⚠ same type
DAZL p.Asn217Asp 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/dazl-p-pro221leu (accessed [today's date]).

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