Is DNAI3 p.Pro3Ala (c.7C>G) pathogenic?

DNAI3 p.Pro3Ala (c.7C>G) is classified Benign in DNAI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0725); Rare (popmax 0.949%, nfe).

How common is DNAI3 p.Pro3Ala (c.7C>G) in the general population?

DNAI3 p.Pro3Ala (c.7C>G) is rare (popmax 0.949%, nfe) (gnomAD).

What do computational predictors say about DNAI3 p.Pro3Ala (c.7C>G)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

DNAI3 p.Pro3Ala

c.7C>G · rs148724953 · VCV787527

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.949%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -8.16	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 -0.051	GERP -2.4, phastCons 0.001
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.45 · regional, not allelic
Overall
CADD	14.56	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 0.949% European (non-Finnish) · 11,188/1,179,280 alleles

Filtering AF 0.934% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.928%

Overall 0.787% 12,688/1,611,320 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.949%	105
Finnishnot grpmax-eligible	0.704%	142
Remaining individualsnot grpmax-eligible	0.647%	154
Ashkenazi Jewishnot grpmax-eligible	0.444%	225
Amishnot grpmax-eligible	0.439%	228
Admixed American	0.436%	230
Middle Eastern	0.215%	466
African / African-American	0.148%	673
South Asian	0.142%	705

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: DNAI3
Protein: p.Pro3Ala
Coding: c.7C>G
MANE Select: NM_145172
dbSNP: rs148724953
Type: single nucleotide variant
Location: chr1:85071948 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.17 · 1 PDB
Residue 3: the 'disordered' region

Full DNAI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAI3 c.1350+6C>A Benign ★★ same type
DNAI3 p.Ala308Thr Benign ★★ same type
DNAI3 p.Arg79= Benign ★★ same type
DNAI3 p.Asp577= Benign ★★ same type
DNAI3 p.Glu458= Likely benign ★★ same type
DNAI3 p.Glu751= Benign ★★ same type
DNAI3 p.His788= Benign ★★ same type
DNAI3 p.His817= 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/dnai3-p-pro3ala (accessed [today's date]).

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