Is DZIP1L p.Ser426Phe (c.1277C>T) pathogenic?

DZIP1L p.Ser426Phe (c.1277C>T) is classified Benign in DZIP1L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-02). AlphaMissense: likely benign (0.1109); Low-frequency (popmax 1.76%, sas).

How common is DZIP1L p.Ser426Phe (c.1277C>T) in the general population?

DZIP1L p.Ser426Phe (c.1277C>T) is low-frequency (popmax 1.76%, sas) (gnomAD).

What do computational predictors say about DZIP1L p.Ser426Phe (c.1277C>T)?

AlphaMissense predicts likely benign (score 0.1109) — an in-silico prediction, not a clinical call.

DZIP1L p.Ser426Phe

c.1277C>T · rs149313849 · VCV1566046

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1109 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.76%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1109	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -8.37	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 8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 41 kb · p 0.44 · regional, not allelic
Overall
CADD	23.3	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 1.76% South Asian · 1,607/91,060 alleles

Filtering AF 1.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.66%

Overall 0.105% 1,700/1,613,898 alleles · low-frequency exomes 1,608/1,461,536 · genomes 92/152,362 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.76%	57
Remaining individualsnot grpmax-eligible	0.0992%	1,008
Middle Eastern	0.0834%	1,198
African / African-American	0.00533%	18,764
East Asian	0.00223%	44,876
European (non-Finnish)	0.0017%	58,993
Admixed American	0.00167%	60,024

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: DZIP1L
Protein: p.Ser426Phe
Coding: c.1277C>T
MANE Select: NM_173543
dbSNP: rs149313849
Type: single nucleotide variant
Location: chr3:138080578 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.03
Residue 426: a modified residue (phosphoserine); a UniProt-annotated variant site (in pkd5)

Full DZIP1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DZIP1L p.Glu358Ter Pathogenic/Likely pathogenic ★★ same type
DZIP1L p.Ala190Val Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg124Cys Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg131Cys Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg233Gln Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg37His Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg48Trp Uncertain significance ★★ ⚠ same type
DZIP1L p.Arg500Gln 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/dzip1l-p-ser426phe (accessed [today's date]).

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