Is DNAI7 p.Leu50Pro (c.149T>C) pathogenic?

DNAI7 p.Leu50Pro (c.149T>C) is classified Uncertain significance in DNAI7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely pathogenic (0.8175); Very rare (popmax 0.0039%, nfe).

How common is DNAI7 p.Leu50Pro (c.149T>C) in the general population?

DNAI7 p.Leu50Pro (c.149T>C) is very rare (popmax 0.0039%, nfe) (gnomAD).

What do computational predictors say about DNAI7 p.Leu50Pro (c.149T>C)?

AlphaMissense predicts likely pathogenic (score 0.8175) — an in-silico prediction, not a clinical call.

DNAI7 p.Leu50Pro

c.149T>C · rs143690815 · VCV3084340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8175 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0039%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8175	likely pathogenic · top 6% in DNAI7
REVEL	0.154	moderately benign-leaning
SaProt	LLR -15.25	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 87 kb · p 0.044 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L44P vs ClinVar L50P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0039% European (non-Finnish) · 46/1,179,744 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00298% 48/1,613,038 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0039%	25,647
Admixed American	0.00167%	59,974
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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: DNAI7
Protein: p.Leu50Pro
Coding: c.149T>C
MANE Select: NM_018272
dbSNP: rs143690815
Type: single nucleotide variant
Location: chr12:25158521 (GRCh38)
Gene constraint: LOEUF 1.282 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.01 · 1 PDB

Full DNAI7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI7 c.300+1G>A Uncertain significance ★ same type
DNAI7 p.Ala570Thr Uncertain significance ★ ⚠ same type
DNAI7 p.Ala65Thr Uncertain significance ★ ⚠ same type
DNAI7 p.Arg235Gly Uncertain significance ★ ⚠ same type
DNAI7 p.Arg311Gly Uncertain significance ★ ⚠ same type
DNAI7 p.Arg348Gln Uncertain significance ★ ⚠ same type
DNAI7 p.Arg39Cys Uncertain significance ★ ⚠ same type
DNAI7 p.Arg54Gln 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/dnai7-p-leu50pro (accessed [today's date]).

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