Is DORIP1 p.Ser148Phe (c.443C>T) pathogenic?

DORIP1 p.Ser148Phe (c.443C>T) is classified Uncertain significance in DORIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.295); Very rare (popmax 0.00695%, nfe).

How common is DORIP1 p.Ser148Phe (c.443C>T) in the general population?

DORIP1 p.Ser148Phe (c.443C>T) is very rare (popmax 0.00695%, nfe) (gnomAD).

What do computational predictors say about DORIP1 p.Ser148Phe (c.443C>T)?

AlphaMissense predicts likely benign (score 0.295) — an in-silico prediction, not a clinical call.

DORIP1 p.Ser148Phe

c.443C>T · rs560702536 · VCV2398402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.295 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.295	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.8	GERP 0.93, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 5,111 bp · p 0.9 · regional, not allelic
Overall
CADD	25.1	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

Grpmax group 0.00695% European (non-Finnish) · 82/1,179,878 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00533% 86/1,613,856 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,389
Remaining individualsnot grpmax-eligible	0.0032%	31,248
South Asian	0.0022%	45,515

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: DORIP1
Protein: p.Ser148Phe
Coding: c.443C>T
MANE Select: NM_001017923
dbSNP: rs560702536
Type: single nucleotide variant
Location: chr14:44900878 (GRCh38)
Structure: AlphaFold pLDDT 83.15

Full DORIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DORIP1 p.Glu309Asp Benign ★★ same type
DORIP1 p.Leu66= Benign ★★ same type
DORIP1 p.Leu282Phe Uncertain significance ★ ⚠ same type
DORIP1 p.Pro177Leu Benign ★ same type
DORIP1 p.Ser234Phe 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/dorip1-p-ser148phe (accessed [today's date]).

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